Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Mohamed Hassan
 -- 2172 2023-06-21 15:56:55 |
2 format
Jason Zhu
 Meta information modification 2172 2023-06-25 04:13:47 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Kharouf, N.; Flanagan, T.W.; Hassan, S.; Shalaby, H.; Khabaz, M.; Hassan, S.; Megahed, M.; Haikel, Y.; Santourlidis, S.; Hassan, M. Tumor Microenvironment in Melanoma Treatment. Encyclopedia. Available online: https://encyclopedia.pub/entry/45944 (accessed on 27 July 2024).
Kharouf N, Flanagan TW, Hassan S, Shalaby H, Khabaz M, Hassan S, et al. Tumor Microenvironment in Melanoma Treatment. Encyclopedia. Available at: https://encyclopedia.pub/entry/45944. Accessed July 27, 2024.
Kharouf, Naji, Thomas W. Flanagan, Sofie-Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah-Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan. "Tumor Microenvironment in Melanoma Treatment" Encyclopedia, https://encyclopedia.pub/entry/45944 (accessed July 27, 2024).
Kharouf, N., Flanagan, T.W., Hassan, S., Shalaby, H., Khabaz, M., Hassan, S., Megahed, M., Haikel, Y., Santourlidis, S., & Hassan, M. (2023, June 21). Tumor Microenvironment in Melanoma Treatment. In Encyclopedia. https://encyclopedia.pub/entry/45944
Kharouf, Naji, et al. "Tumor Microenvironment in Melanoma Treatment." Encyclopedia. Web. 21 June, 2023.
Tumor Microenvironment in Melanoma Treatment
Edit
This entry is adapted from the peer-reviewed paper 10.3390/cancers15123147

The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic tumor cells, but it also contains supporting stroma, ECM, and soluble molecules. Melanoma cells are continuously in interaction with the components of the microenvironment.

tumor microenvironment stromal cells melanoma resistance targeted therapy

1. Introduction

Melanoma is one of the most common skin cancers, and it is notorious for its heterogeneity and propensity to metastasize to distant organs [1][2]. Although the treatment options of melanoma have improved in recent years, patients with advanced malignant melanoma still have poor prognosis, as measured by progression-free and overall survival [3].
Molecularly targeted therapies are characterized by their specificity to interfere with key molecules of aberrant signaling pathways, particularly those of tumor growth and survival. Over 60% of primary cutaneous melanomas and over 50% of metastatic melanomas harbor the activating murine sarcoma viral oncogene homolog B (BRAF) mutation [4][5]. To that end, the continuous activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling by the BRAFV600E mutation is common and independent from extracellular stimulation [6][7]. Melanoma is a tumor mass that contains supporting stroma (fibroblasts, endothelial cells, and immune cells), the extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles), rather than a mass of monolithic tumor cells.

2. Tumor Microenvironment as Therapeutic Target in Melanoma Treatment

Apart from its adverse effects, chemotherapeutic agents remain the best option for cancer therapy to date. Depending on the tumor stage and patient tolerability, chemotherapy can be given alone or in combination with surgery or radiotherapy [8][9]. The discovery of active mutations, which are involved in tumor initiation and development, such as epidermal growth factor receptor (EGFR), p53, c-Kit and BRAF [10][11], compelled researchers to extensively study the reliability of such mutations as selective therapeutic targets [12][13][14]. Although the successful targeting of these mutations improves overall survival of melanoma patients, acquired tumor resistance develops and increases continuously [15][16]. Consequently, tumor relapse and low life quality of patients are common.
During tumor development, cancer cells and the components of the tumor microenvironment are continually adapting to the environmental conditions to promote tumor growth, progression, and treatment resistance [17].
Tumor microenvironment components play a significant role in cancer progression, maintenance, and resistance to anticancer agents [18][19]. The crosstalk between tumor cells and their microenvironment is essential for acquiring and maintaining tumor cell characteristics, such as sustaining proliferative signaling, resisting cell death, inducing angiogenesis, activating invasion, metastasis, triggering tumor-promoting inflammation, and avoiding immune destruction [20][21][22]. This dependence on the tumor microenvironment offers an opportunity for the development of therapeutic approaches by targeting the components of the tumor microenvironment or their dependent signaling pathways. Based on the increased understanding of the crucial roles of the tumor microenvironment on tumor development and therapeutic resistance, many efforts have been made to target tumor microenvironment components for therapeutic benefit in cancer patients [23]. Importantly, targeting the components of the tumor microenvironment has a significant therapeutic advantage over the direct targeting of cancer cells, as cancer cells are infamous for their genomic instability that is a main cause for the development of drug resistance [24][25]. In contrast, the non-tumor cells of the tumor microenvironment are genetically more stable in nature and more susceptible [26].

2.1. Cancer-Associated Fibroblasts as Therapeutic Target

Over the recent decade, accumulating evidence revealed that CAFs, the major component of stroma in malignancies, play an essential role in tumor proliferation, progression, and treatment resistance [23][27]. Thus, CAFs are suggested to be a potential therapeutic target for the treatment of different tumor types including melanoma. Many drugs targeting CAFs have been developed and tested in preclinical and/or clinical studies. The most identified targets of CAFs are the fibroblast activation protein (FAP), vitamin D receptor (VDR), and platelet-derived growth factor receptor (PDGRF) [28][29][30].
FAP is a serine protease with dual enzymatic activities and is overexpressed in CAFs and in many other tumor types [31]. The G-protein-coupled receptor 77 (GPR77) is a potential FAP surface target and is specifically expressed in CAFs [28][29][30]. In addition to its important role in tumor development, the overexpression of FAP on CAFs is mostly associated with poor prognosis [32][33].
Accumulating evidence suggests that vitamin D does not only suppress cancer cells but also contributes to the modulation of tumor stromal cell genes and triggers tumor angiogenesis, progression, and metastasis [34][35]. These observations suggest that the vitamin D receptor is a promising target for the treatment of tumors such as melanoma. 
Several studies suggested that an important role exists for PDGF in the regulation of the recruitment and phenotypic character of the tumor stroma [36][37]. PDGF-BB has been shown to trigger the formation of growth-promoting stroma in melanoma [36][37]. Inhibition of vascular endothelial growth factor-A (VEGF-A) production promotes tumor cells to secrete PDGF-AA to attract stromal fibroblasts, which can be stimulated to produce VEGF-A and induce angiogenesis [38][39]. To that end, PDGRF is essential in promoting tumor growth by both direct growth stimulatory effects and promotion of angiogenesis and pericyte recruitment [40][41], and it is therefore a promising therapeutic target for tumor treatment.

2.2. Tumor-Associated Macrophages as Therapeutic Target

Tumor-associated macrophages (TAMs) have also emerged as therapeutic targets in melanoma treatment. TAMs belong to stromal cells and are abundant in the tumor microenvironment [42][43]. TAMs are mostly associated with poor clinical outcomes in cancer patients [44][45]. Accordingly, colony-stimulating factor 1 receptor (CSF1R) signaling has gained more attention as a therapeutic target. CSF1/CSF1R has been reported to play a central role in the proliferation, differentiation, and function of macrophages [46][47]. Therefore, inhibition of CSF1R signaling is expected to block the function of TAMs. Consequently, several inhibitors (PLX3397, JNJ-40346527, PLX7486, and ARRY-382) and neutralizing antibodies (RG7155, IMC-CS4, and FPA008) have been developed and tested for their clinical relevance as CSF1R inhibitor-based therapies [46][48]. Many preclinical and clinical investigations have demonstrated that inhibition of CSF1R results in the depletion of TAMs and microglia [49].

2.3. Tumor-Associated Neutrophils

Tumor-associated neutrophils (TANs) are also therapeutic targets in melanoma treatment. TANs originate from myeloid precursors and are the most abundant population of leukocytes as well as the first responders of innate immunity [28][50]. TANs are one of the most important stromal cells in the tumor microenvironment and play active roles in tumor progression and metastatic dissemination [51][52] TANs mediate their pro-tumor roles by stimulating ECM and inflammation in the tumor microenvironment [53]. TANs are characterized by their ability to release granules containing various proteases, such as matrix metalloprotease 9 (MMP-9) [54][55] and neutrophil elastase [56][57]. Consequently, TANs can remodel ECM and promote tumor invasion [45][58]. In addition to the production of proinflammatory cytokines/chemokines, TANs also produce immunosuppressive factors, including arginase 1 and TGF-β [59]. These immunosuppressive factors are mainly involved in the suppression of adaptive immunity [60] as well as in the release of HGF to promote tumor progression [61]. Thus, targeting TANs is expected to be a potential therapeutic strategy for tumor treatment [62]. One of the most promising targets is the chemokine receptor 2 (CXCR2), which is known to be a critical regulator for neutrophil mobilization [63]. Preventing the interaction between CXCR2 and its ligand (CXCL8) by small molecular inhibitors or antibodies has been shown to exert anti-tumor activities and improves the treatment efficacy of chemotherapy [63][64]. Several clinical trials such as SX-682 have been suggested as potent inhibitors of CXCR1/2. SX-682 has been tested for its clinical relevance in several studies [65]. SX-682 can block tumor cells by attracting myeloid-derived suppressor cells (MDSCs), which increases therapeutic efficacy when combined with immunotherapies [65].

3. Tumor-Promoting Chronic Inflammation as Therapeutic Target for Melanoma Treatment

Inflammation is a consequence of the innate immune response reacting to disturbed tissue homeostasis. Chronic inflammation is one of the common hallmarks of cancer and plays an essential role in the enhancement of tumor development and progression [66][67]. Thus, targeting inflammation is expected to be a promising approach for cancer therapy. Data obtained from a large population study revealed that aspirin is an anti-inflammatory drug found to significantly reduce cancer risk [68][69]. Both macrophages and tumor cells are characterized by their potency to produce proinflammatory cytokines and inflammatory mediators and thereby sustain tumor cell proliferation and survival [70][71], immune evasion [72], angiogenesis [73][74], ECM remodeling [75][76], metastasis [77], chemoresistance [73][78], as well as radio-resistance [79]. To that end, targeting the key mediators of proinflammatory pathways and/or the main regulators (e.g., NF-κB and STAT3) of inflammatory cytokines (e.g., IL-1, TNF, and IL-6) is expected to inhibit cancer-promoting inflammation. Unfortunately, few antibodies/inhibitors exhibited anti-tumor activities in preclinical studies; thus, only a few candidates are under investigation in early-stage clinical trials [80][81]. Therefore, the main challenge of targeting inflammation is how to develop selective anti-inflammatory approaches without impairing anti-tumor immunity.
Other components of the tumor microenvironment can function as targets for melanoma treatment. These include B lymphocytes, regulatory T cells (Treg), adipocytes, mesenchymal stem cells, and exosomes [82][83]. These tumor microenvironment components have been shown to influence tumor progression and therapeutic responses [84]. Tregs are characterized by the expression of the transcription factor fork head box protein p3 (Foxp3) that is involved in the suppression of anticancer immunity [85][86][87]. Consequently, the protective immunosurveillance of tumors can be impaired, resulting in the loss of effective antitumor immune responses. Functionally, the tumor microenvironment can trigger the suppression of Tregs by the upregulation of immune checkpoint proteins. Thus, targeting immune checkpoint molecules (e.g., CTLA-4, TIGIT, PD-1, and GITR) on Tregs may have a therapeutic impact on the treatment of melanoma.
The role of inhibitory receptors in the regulation of both innate and adaptive immunity in chronic viral infections and cancer has been studied [88][89]. Chronic antigen stimulation mainly results in the modulation of T cell dysfunction and the upregulation of inhibitory receptors such as programmed cell death-1 (PD-1) and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) [90][91]. In addition to the expression of the ligands of the inhibitory receptors by tumor cells, the tumor microenvironment contains the required antigen-presenting cells (APCs) [92][93]. TIGIT has been reported to play a critical role in the reduction of both adaptive and innate immunity against tumors [90][91]. The clinical relevance of monoclonal antibodies targeting the inhibitory receptors has been reported in several studies [94].
T lymphocyte-associated antigen 4 (CTLA-4) is one of the first identified inhibitors of immune checkpoint on Tregs. Targeting CTLA-4 by anti-CTLA-4 antibodies has been shown to block the tumor suppressive function of Tregs and ultimately to release the cytotoxicity function of effector cells.
Programmed cell death 1 (PD-1) signaling is known to be hijacked by cancer cells to escape immune surveillance [95][96][97]. The intrinsic expression of PD-1 has been reported to contribute to the development of tumor monoresistance [98][99]. In melanoma cells, the activation of PD-1 by its ligand PD-L1 has been shown to trigger the activation of downstream mammalian targets of rapamycin signaling leading to tumor growth [100]. Thus, targeting the PD-1/PD-L1 axis has shown enormous success in a variety of human cancers [101][102]. Due to its durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, antibody-mediated blockade of PD-L1 is clinically relevant.
In the last two decades, the treatment of a variety of malignancies based on immune checkpoint modulation has been promising compared to available therapeutic modalities. However, checkpoint modulation has been reported to be less therapeutically effective in cancers with an immunosuppressive microenvironment [103][104]. Although the advent of immunomodulatory agents has led to improved responses in tumor patients, as evidenced by achieving long-lasting tumor remission [105][106], many exhibit brief or no response to available immunomodulatory agents [107][108]. Thus, the development of alternate therapeutic strategies is of great interest. In recent years, the modulation of the tumor microenvironment, in the context of the local metabolites, has been suggested as a promising strategy in cancer immunotherapy [109]. For example, live tumor-targeting bacteria have emerged as a treatment for solid tumors, compared with immunotherapy and targeted therapy [110]. Likewise, the clinical investigation of live engineered bacteria for metabolic modulation has been reported [111].
Oncolytic viruses have also been suggested as a promising alternative therapy for cancer treatment, particularly for refractory cancers with a 5-year survival rate of 5%, such glioblastoma [112]. While viral-mediated oncolysis has been hypothesized to spread to all cancer cells within the tumor, this has not been shown in clinical studies so far. Clinical data revealed that the development of an antiviral immune response and limited antitumor immunity limit the efficiency of virotherapy when utilized as a monotherapy [113][114]. Apart from the abovementioned limitations of virotherapy, the mechanisms of viral infection, replication, and tumor necrosis have the potential to destruct the immunosuppressive tumor microenvironment and ultimately enhance T cell reactivity against cancer neo-antigens [115].
The advantage of oncolytic virotherapy over checkpoint-protein-based immune therapy is attributed to the ability of oncolytic virotherapy to circumvent the immune evasion mechanisms of the tumor [116][117]. Oncolytic virotherapy can also improve the treatment outcome of tumor patients by the stimulation of host immune system and/or direct lysis of tumor cells.

References

  1. Karras, P.; Bordeu, I.; Pozniak, J.; Nowosad, A.; Pazzi, C.; Van Raemdonck, N.; Landeloos, E.; Van Herck, Y.; Pedri, D.; Bervoets, G.; et al. A cellular hierarchy in melanoma uncouples growth and metastasis. Nature 2022, 610, 190–198.
  2. Motwani, J.; Eccles, M.R. Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis. Genes 2021, 12, 1543.
  3. Weiss, S.A.; Hanniford, D.; Hernando, E.; Osman, I. Revisiting determinants of prognosis in cutaneous melanoma. Cancer 2015, 121, 4108–4123.
  4. Teixido, C.; Castillo, P.; Martinez-Vila, C.; Arance, A.; Alos, L. Molecular Markers and Targets in Melanoma. Cells 2021, 10, 2320.
  5. Ascierto, P.A.; Kirkwood, J.M.; Grob, J.J.; Simeone, E.; Grimaldi, A.M.; Maio, M.; Palmieri, G.; Testori, A.; Marincola, F.M.; Mozzillo, N. The role of BRAF V600 mutation in melanoma. J. Transl. Med. 2012, 10, 85.
  6. Czarnecka, A.M.; Bartnik, E.; Fiedorowicz, M.; Rutkowski, P. Targeted Therapy in Melanoma and Mechanisms of Resistance. Int. J. Mol. Sci. 2020, 21, 4576.
  7. Dankner, M.; Rose, A.A.N.; Rajkumar, S.; Siegel, P.M.; Watson, I.R. Classifying BRAF alterations in cancer: New rational therapeutic strategies for actionable mutations. Oncogene 2018, 37, 3183–3199.
  8. van der Valk, M.J.M.; Marijnen, C.A.M.; van Etten, B.; Dijkstra, E.A.; Hilling, D.E.; Kranenbarg, E.M.; Putter, H.; Roodvoets, A.G.H.; Bahadoer, R.R.; Fokstuen, T.; et al. Compliance and tolerability of short-course radiotherapy followed by preoperative chemotherapy and surgery for high-risk rectal cancer - Results of the international randomized RAPIDO-trial. Radiother. Oncol. 2020, 147, 75–83.
  9. Li, R.; Wang, Q.; Zhang, B.; Yuan, Y.; Xie, W.; Huang, X.; Zhou, C.; Zhang, S.; Niu, S.; Chang, H.; et al. Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases. BMC Cancer 2021, 21, 1333.
  10. Yamada, T.; Matsuda, A.; Takahashi, G.; Iwai, T.; Takeda, K.; Ueda, K.; Kuriyama, S.; Koizumi, M.; Shinji, S.; Yokoyama, Y.; et al. Emerging RAS, BRAF, and EGFR mutations in cell-free DNA of metastatic colorectal patients are associated with both primary and secondary resistance to first-line anti-EGFR therapy. Int. J. Clin. Oncol. 2020, 25, 1523–1532.
  11. Fattore, L.; Marra, E.; Pisanu, M.E.; Noto, A.; de Vitis, C.; Belleudi, F.; Aurisicchio, L.; Mancini, R.; Torrisi, M.R.; Ascierto, P.A.; et al. Activation of an early feedback survival loop involving phospho-ErbB3 is a general response of melanoma cells to RAF/MEK inhibition and is abrogated by anti-ErbB3 antibodies. J. Transl. Med. 2013, 11, 180.
  12. Wang, M.; Liu, M.; Huang, Y.; Wang, Z.; Wang, Y.; He, K.; Bai, R.; Ying, T.; Zheng, Y. Differential Gene Expression and Methylation Analysis of Melanoma in TCGA Database to Further Study the Expression Pattern of KYNU in Melanoma. J. Pers. Med. 2022, 12, 1209.
  13. Delyon, J.; Lebbe, C.; Dumaz, N. Targeted therapies in melanoma beyond BRAF: Targeting NRAS-mutated and KIT-mutated melanoma. Curr. Opin. Oncol. 2020, 32, 79–84.
  14. Ponti, G.; Manfredini, M.; Greco, S.; Pellacani, G.; Depenni, R.; Tomasi, A.; Maccaferri, M.; Cascinu, S. BRAF, NRAS and C-KIT Advanced Melanoma: Clinico-pathological Features, Targeted-Therapy Strategies and Survival. Anticancer Res. 2017, 37, 7043–7048.
  15. Turner, E.; Chen, L.; Foulke, J.G.; Gu, Z.; Tian, F. CRISPR/Cas9 Edited RAS & MEK Mutant Cells Acquire BRAF and MEK Inhibitor Resistance with MEK1 Q56P Restoring Sensitivity to MEK/BRAF Inhibitor Combo and KRAS G13D Gaining Sensitivity to Immunotherapy. Cancers 2022, 14, 5449.
  16. Sun, C.; Wang, L.; Huang, S.; Heynen, G.J.; Prahallad, A.; Robert, C.; Haanen, J.; Blank, C.; Wesseling, J.; Willems, S.M.; et al. Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature 2014, 508, 118–122.
  17. Walbrecq, G.; Lecha, O.; Gaigneaux, A.; Fougeras, M.R.; Philippidou, D.; Margue, C.; Tetsi Nomigni, M.; Bernardin, F.; Dittmar, G.; Behrmann, I.; et al. Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles. Cancers 2020, 12, 692.
  18. Mimeault, M.; Batra, S.K. Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells. J. Cell Mol. Med. 2013, 17, 30–54.
  19. Quail, D.F.; Joyce, J.A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 2013, 19, 1423–1437.
  20. Marzagalli, M.; Ebelt, N.D.; Manuel, E.R. Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment. Semin. Cancer Biol. 2019, 59, 236–250.
  21. Avagliano, A.; Fiume, G.; Pelagalli, A.; Sanità, G.; Ruocco, M.R.; Montagnani, S.; Arcucci, A. Metabolic Plasticity of Melanoma Cells and Their Crosstalk With Tumor Microenvironment. Front. Oncol. 2020, 10, 722.
  22. Elia, A.R.; Caputo, S.; Bellone, M. Immune Checkpoint-Mediated Interactions Between Cancer and Immune Cells in Prostate Adenocarcinoma and Melanoma. Front. Immunol. 2018, 9, 1786.
  23. Bagaev, A.; Kotlov, N.; Nomie, K.; Svekolkin, V.; Gafurov, A.; Isaeva, O.; Osokin, N.; Kozlov, I.; Frenkel, F.; Gancharova, O.; et al. Conserved pan-cancer microenvironment subtypes predict response to immunotherapy. Cancer Cell 2021, 39, 845–865.e847.
  24. Strub, T.; Giuliano, S.; Ye, T.; Bonet, C.; Keime, C.; Kobi, D.; Le Gras, S.; Cormont, M.; Ballotti, R.; Bertolotto, C.; et al. Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma. Oncogene 2011, 30, 2319–2332.
  25. Dharanipragada, P.; Zhang, X.; Liu, S.; Lomeli, S.H.; Hong, A.; Wang, Y.; Yang, Z.; Lo, K.Z.; Vega-Crespo, A.; Ribas, A.; et al. Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma. Cancer Discov. 2023, 13, 880–909.
  26. Sensebé, L. Beyond genetic stability of mesenchymal stromal cells. Cytotherapy 2013, 15, 1307–1308.
  27. Thompson, B.J. YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy. Bioessays 2020, 42, e1900162.
  28. Fujimura, T. Stromal Factors as a Target for Immunotherapy in Melanoma and Non-Melanoma Skin Cancers. Int. J. Mol. Sci. 2022, 23, 4044.
  29. Bejarano, L.; Jordāo, M.J.C.; Joyce, J.A. Therapeutic Targeting of the Tumor Microenvironment. Cancer Discov. 2021, 11, 933–959.
  30. Zhou, L.; Yang, K.; Andl, T.; Wickett, R.R.; Zhang, Y. Perspective of Targeting Cancer-Associated Fibroblasts in Melanoma. J. Cancer 2015, 6, 717–726.
  31. Hamson, E.J.; Keane, F.M.; Tholen, S.; Schilling, O.; Gorrell, M.D. Understanding fibroblast activation protein (FAP): Substrates, activities, expression and targeting for cancer therapy. Proteomics Clin. Appl. 2014, 8, 454–463.
  32. Zboralski, D.; Hoehne, A.; Bredenbeck, A.; Schumann, A.; Nguyen, M.; Schneider, E.; Ungewiss, J.; Paschke, M.; Haase, C.; von Hacht, J.L.; et al. Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy. Eur. J. Nucl. Med. Mol. Imaging 2022, 49, 3651–3667.
  33. Zhang, Y.; Ertl, H.C. Depletion of FAP+ cells reduces immunosuppressive cells and improves metabolism and functions CD8+T cells within tumors. Oncotarget 2016, 7, 23282–23299.
  34. Brożyna, A.A.; Hoffman, R.M.; Slominski, A.T. Relevance of Vitamin D in Melanoma Development, Progression and Therapy. Anticancer Res. 2020, 40, 473–489.
  35. Nemazannikova, N.; Antonas, K.; Dass, C.R. Role of vitamin D metabolism in cutaneous tumour formation and progression. J. Pharm. Pharmacol. 2013, 65, 2–10.
  36. Zheng, Y.; Yamamoto, S.; Ishii, Y.; Sang, Y.; Hamashima, T.; Van De, N.; Nishizono, H.; Inoue, R.; Mori, H.; Sasahara, M. Glioma-Derived Platelet-Derived Growth Factor-BB Recruits Oligodendrocyte Progenitor Cells via Platelet-Derived Growth Factor Receptor-α and Remodels Cancer Stroma. Am. J. Pathol. 2016, 186, 1081–1091.
  37. Lederle, W.; Stark, H.J.; Skobe, M.; Fusenig, N.E.; Mueller, M.M. Platelet-derived growth factor-BB controls epithelial tumor phenotype by differential growth factor regulation in stromal cells. Am. J. Pathol. 2006, 169, 1767–1783.
  38. Onimaru, M.; Yonemitsu, Y. Angiogenic and lymphangiogenic cascades in the tumor microenvironment. Front. Biosci. 2011, 3, 216–225.
  39. Hawryluk, G.W.; Mothe, A.; Wang, J.; Wang, S.; Tator, C.; Fehlings, M.G. An in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell transplantation for spinal cord injury. Stem Cells Dev. 2012, 21, 2222–2238.
  40. Di Desidero, T.; Orlandi, P.; Fioravanti, A.; Alì, G.; Cremolini, C.; Loupakis, F.; Gentile, D.; Banchi, M.; Cucchiara, F.; Antoniotti, C.; et al. Chemotherapeutic and antiangiogenic drugs beyond tumor progression in colon cancer: Evaluation of the effects of switched schedules and related pharmacodynamics. Biochem. Pharmacol. 2019, 164, 94–105.
  41. Benjamin, R.S.; Schöffski, P.; Hartmann, J.T.; Van Oosterom, A.; Bui, B.N.; Duyster, J.; Schuetze, S.; Blay, J.Y.; Reichardt, P.; Rosen, L.S.; et al. Efficacy and safety of motesanib, an oral inhibitor of VEGF, PDGF, and Kit receptors, in patients with imatinib-resistant gastrointestinal stromal tumors. Cancer Chemother. Pharmacol. 2011, 68, 69–77.
  42. Chen, Y.; McAndrews, K.M.; Kalluri, R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat. Rev. Clin. Oncol. 2021, 18, 792–804.
  43. Pan, Y.; Yu, Y.; Wang, X.; Zhang, T. Tumor-Associated Macrophages in Tumor Immunity. Front. Immunol. 2020, 11, 583084.
  44. Zhang, H.; Li, R.; Cao, Y.; Gu, Y.; Lin, C.; Liu, X.; Lv, K.; He, X.; Fang, H.; Jin, K.; et al. Poor Clinical Outcomes and Immunoevasive Contexture in Intratumoral IL-10-Producing Macrophages Enriched Gastric Cancer Patients. Ann. Surg. 2022, 275, e626–e635.
  45. Hwang, I.; Kim, J.W.; Ylaya, K.; Chung, E.J.; Kitano, H.; Perry, C.; Hanaoka, J.; Fukuoka, J.; Chung, J.Y.; Hewitt, S.M. Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients. J. Transl. Med. 2020, 18, 443.
  46. Fujiwara, T.; Yakoub, M.A.; Chandler, A.; Christ, A.B.; Yang, G.; Ouerfelli, O.; Rajasekhar, V.K.; Yoshida, A.; Kondo, H.; Hata, T.; et al. CSF1/CSF1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-cell Infiltration in the Sarcoma Microenvironment. Mol. Cancer Ther. 2021, 20, 1388–1399.
  47. Pridans, C.; Sauter, K.A.; Irvine, K.M.; Davis, G.M.; Lefevre, L.; Raper, A.; Rojo, R.; Nirmal, A.J.; Beard, P.; Cheeseman, M.; et al. Macrophage colony-stimulating factor increases hepatic macrophage content, liver growth, and lipid accumulation in neonatal rats. Am. J. Physiol. Gastrointest. Liver Physiol. 2018, 314, G388–G398.
  48. Kumar, V.; Donthireddy, L.; Marvel, D.; Condamine, T.; Wang, F.; Lavilla-Alonso, S.; Hashimoto, A.; Vonteddu, P.; Behera, R.; Goins, M.A.; et al. Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors. Cancer Cell 2017, 32, 654–668.e655.
  49. Pyonteck, S.M.; Akkari, L.; Schuhmacher, A.J.; Bowman, R.L.; Sevenich, L.; Quail, D.F.; Olson, O.C.; Quick, M.L.; Huse, J.T.; Teijeiro, V.; et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat. Med. 2013, 19, 1264–1272.
  50. Pylaeva, E.; Harati, M.D.; Spyra, I.; Bordbari, S.; Strachan, S.; Thakur, B.K.; Höing, B.; Franklin, C.; Skokowa, J.; Welte, K.; et al. NAMPT signaling is critical for the proangiogenic activity of tumor-associated neutrophils. Int. J. Cancer 2019, 144, 136–149.
  51. Zhou, S.L.; Zhou, Z.J.; Hu, Z.Q.; Huang, X.W.; Wang, Z.; Chen, E.B.; Fan, J.; Cao, Y.; Dai, Z.; Zhou, J. Tumor-Associated Neutrophils Recruit Macrophages and T-Regulatory Cells to Promote Progression of Hepatocellular Carcinoma and Resistance to Sorafenib. Gastroenterology 2016, 150, 1646–1658.
  52. Jaillon, S.; Ponzetta, A.; Di Mitri, D.; Santoni, A.; Bonecchi, R.; Mantovani, A. Neutrophil diversity and plasticity in tumour progression and therapy. Nat. Rev. Cancer 2020, 20, 485–503.
  53. Galdiero, M.R.; Bonavita, E.; Barajon, I.; Garlanda, C.; Mantovani, A.; Jaillon, S. Tumor associated macrophages and neutrophils in cancer. Immunobiology 2013, 218, 1402–1410.
  54. Vannitamby, A.; Seow, H.J.; Anderson, G.; Vlahos, R.; Thompson, M.; Steinfort, D.; Irving, L.B.; Bozinovski, S. Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment. Thorax 2017, 72, 1140–1143.
  55. Bekes, E.M.; Schweighofer, B.; Kupriyanova, T.A.; Zajac, E.; Ardi, V.C.; Quigley, J.P.; Deryugina, E.I. Tumor-recruited neutrophils and neutrophil TIMP-free MMP-9 regulate coordinately the levels of tumor angiogenesis and efficiency of malignant cell intravasation. Am. J. Pathol. 2011, 179, 1455–1470.
  56. Gong, L.; Cumpian, A.M.; Caetano, M.S.; Ochoa, C.E.; De la Garza, M.M.; Lapid, D.J.; Mirabolfathinejad, S.G.; Dickey, B.F.; Zhou, Q.; Moghaddam, S.J. Promoting effect of neutrophils on lung tumorigenesis is mediated by CXCR2 and neutrophil elastase. Mol. Cancer 2013, 12, 154.
  57. Mittendorf, E.A.; Alatrash, G.; Qiao, N.; Wu, Y.; Sukhumalchandra, P.; St John, L.S.; Philips, A.V.; Xiao, H.; Zhang, M.; Ruisaard, K.; et al. Breast cancer cell uptake of the inflammatory mediator neutrophil elastase triggers an anticancer adaptive immune response. Cancer Res. 2012, 72, 3153–3162.
  58. Hurt, B.; Schulick, R.; Edil, B.; El Kasmi, K.C.; Barnett, C. Cancer-promoting mechanisms of tumor-associated neutrophils. Am. J. Surg. 2017, 214, 938–944.
  59. Lim, C.L.; Lin, V.C. Estrogen markedly reduces circulating low-density neutrophils and enhances pro-tumoral gene expression in neutrophil of tumour-bearing mice. BMC Cancer 2021, 21, 1017.
  60. Mishalian, I.; Bayuh, R.; Eruslanov, E.; Michaeli, J.; Levy, L.; Zolotarov, L.; Singhal, S.; Albelda, S.M.; Granot, Z.; Fridlender, Z.G. Neutrophils recruit regulatory T-cells into tumors via secretion of CCL17--a new mechanism of impaired antitumor immunity. Int. J. Cancer 2014, 135, 1178–1186.
  61. Mizuno, R.; Kawada, K.; Itatani, Y.; Ogawa, R.; Kiyasu, Y.; Sakai, Y. The Role of Tumor-Associated Neutrophils in Colorectal Cancer. Int. J. Mol. Sci. 2019, 20, 529.
  62. Zhao, Y.; Rahmy, S.; Liu, Z.; Zhang, C.; Lu, X. Rational targeting of immunosuppressive neutrophils in cancer. Pharmacol. Ther. 2020, 212, 107556.
  63. Wang, Y.; Dembowsky, K.; Chevalier, E.; Stüve, P.; Korf-Klingebiel, M.; Lochner, M.; Napp, L.C.; Frank, H.; Brinkmann, E.; Kanwischer, A.; et al. C-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-Regulatory Function. Circulation 2019, 139, 1798–1812.
  64. Shibata, F.; Konishi, K.; Nakagawa, H. Chemokine receptor CXCR2 activates distinct pathways for chemotaxis and calcium mobilization. Biol. Pharm. Bull. 2002, 25, 1217–1219.
  65. Greene, S.; Robbins, Y.; Mydlarz, W.K.; Huynh, A.P.; Schmitt, N.C.; Friedman, J.; Horn, L.A.; Palena, C.; Schlom, J.; Maeda, D.Y.; et al. Inhibition of MDSC Trafficking with SX-682, a CXCR1/2 Inhibitor, Enhances NK-Cell Immunotherapy in Head and Neck Cancer Models. Clin. Cancer Res. 2020, 26, 1420–1431.
  66. Tengesdal, I.W.; Menon, D.R.; Osborne, D.G.; Neff, C.P.; Powers, N.E.; Gamboni, F.; Mauro, A.G.; D’Alessandro, A.; Stefanoni, D.; Henen, M.A.; et al. Targeting tumor-derived NLRP3 reduces melanoma progression by limiting MDSCs expansion. Proc. Natl. Acad. Sci. USA 2021, 118, e2000915118.
  67. Liu, Q.; Li, A.; Tian, Y.; Wu, J.D.; Liu, Y.; Li, T.; Chen, Y.; Han, X.; Wu, K. The CXCL8-CXCR1/2 pathways in cancer. Cytokine Growth Factor Rev. 2016, 31, 61–71.
  68. Liebow, M.; Larson, M.C.; Thompson, C.A.; Nowakowski, G.S.; Call, T.G.; Macon, W.R.; Kay, N.E.; Habermann, T.M.; Slager, S.L.; Cerhan, J.R. Aspirin and other nonsteroidal anti-inflammatory drugs, statins and risk of non-Hodgkin lymphoma. Int. J. Cancer 2021, 149, 535–545.
  69. Neill, A.S.; Nagle, C.M.; Protani, M.M.; Obermair, A.; Spurdle, A.B.; Webb, P.M.; Group, A.N.E.C.S. Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: A case-control study, systematic review and meta-analysis. Int. J. Cancer 2013, 132, 1146–1155.
  70. Hao, N.B.; Lü, M.H.; Fan, Y.H.; Cao, Y.L.; Zhang, Z.R.; Yang, S.M. Macrophages in tumor microenvironments and the progression of tumors. Clin. Dev. Immunol. 2012, 2012, 948098.
  71. Klemke, L.; De Oliveira, T.; Witt, D.; Winkler, N.; Bohnenberger, H.; Bucala, R.; Conradi, L.C.; Schulz-Heddergott, R. Hsp90-stabilized MIF supports tumor progression via macrophage recruitment and angiogenesis in colorectal cancer. Cell Death Dis. 2021, 12, 155.
  72. Dong, H.; Strome, S.E.; Salomao, D.R.; Tamura, H.; Hirano, F.; Flies, D.B.; Roche, P.C.; Lu, J.; Zhu, G.; Tamada, K.; et al. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat. Med. 2002, 8, 793–800.
  73. Dallavalasa, S.; Beeraka, N.M.; Basavaraju, C.G.; Tulimilli, S.V.; Sadhu, S.P.; Rajesh, K.; Aliev, G.; Madhunapantula, S.V. The Role of Tumor Associated Macrophages (TAMs) in Cancer Progression, Chemoresistance, Angiogenesis and Metastasis - Current Status. Curr. Med. Chem. 2021, 28, 8203–8236.
  74. Mantovani, A.; Allavena, P.; Sica, A.; Balkwill, F. Cancer-related inflammation. Nature 2008, 454, 436–444.
  75. Velotti, F.; Barchetta, I.; Cimini, F.A.; Cavallo, M.G. Granzyme B in Inflammatory Diseases: Apoptosis, Inflammation, Extracellular Matrix Remodeling, Epithelial-to-Mesenchymal Transition and Fibrosis. Front. Immunol. 2020, 11, 587581.
  76. Chen, Q.; Jin, M.; Yang, F.; Zhu, J.; Xiao, Q.; Zhang, L. Matrix metalloproteinases: Inflammatory regulators of cell behaviors in vascular formation and remodeling. Mediators Inflamm. 2013, 2013, 928315.
  77. Maimon, A.; Levi-Yahid, V.; Ben-Meir, K.; Halpern, A.; Talmi, Z.; Priya, S.; Mizraji, G.; Mistriel-Zerbib, S.; Berger, M.; Baniyash, M.; et al. Myeloid cell-derived PROS1 inhibits tumor metastasis by regulating inflammatory and immune responses via IL-10. J. Clin. Investig. 2021, 131, e126089.
  78. Savant, S.S.; Sriramkumar, S.; O’Hagan, H.M. The Role of Inflammation and Inflammatory Mediators in the Development, Progression, Metastasis, and Chemoresistance of Epithelial Ovarian Cancer. Cancers 2018, 10, 251.
  79. Senobari, Z.; Karimi, G.; Jamialahmadi, K. Ellagitannins, promising pharmacological agents for the treatment of cancer stem cells. Phytother. Res. 2022, 36, 231–242.
  80. Xiao, Y.; Yu, D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol. Ther. 2021, 221, 107753.
  81. Bienkowska, K.J.; Hanley, C.J.; Thomas, G.J. Cancer-Associated Fibroblasts in Oral Cancer: A Current Perspective on Function and Potential for Therapeutic Targeting. Front. Oral Health 2021, 2, 686337.
  82. Arneth, B. Tumor Microenvironment. Medicina 2019, 56, 15.
  83. Anderson, N.M.; Simon, M.C. The tumor microenvironment. Curr. Biol. 2020, 30, R921–R925.
  84. Wu, T.; Dai, Y. Tumor microenvironment and therapeutic response. Cancer Lett. 2017, 387, 61–68.
  85. Togashi, Y.; Shitara, K.; Nishikawa, H. Regulatory T cells in cancer immunosuppression - implications for anticancer therapy. Nat. Rev. Clin. Oncol. 2019, 16, 356–371.
  86. Sato, Y.; Passerini, L.; Piening, B.D.; Uyeda, M.J.; Goodwin, M.; Gregori, S.; Snyder, M.P.; Bertaina, A.; Roncarolo, M.G.; Bacchetta, R. Human-engineered Treg-like cells suppress FOXP3-deficient T cells but preserve adaptive immune responses. Clin. Transl. Immunol. 2020, 9, e1214.
  87. Ding, X.; Peng, C.; Li, Y.; Liu, J.; Song, Y.; Cai, B.; Xiang, M.; Zhang, J.; Wang, Z.; Wang, L. Targeting Inhibition of Foxp3 by MMP2/9 Sensitive Short Peptide Linked P60 Fusion Protein 6(P60-MMPs) to Enhance Antitumor Immunity. Macromol. Biosci. 2020, 20, e2000098.
  88. Sivori, S.; Della Chiesa, M.; Carlomagno, S.; Quatrini, L.; Munari, E.; Vacca, P.; Tumino, N.; Mariotti, F.R.; Mingari, M.C.; Pende, D.; et al. Inhibitory Receptors and Checkpoints in Human NK Cells, Implications for the Immunotherapy of Cancer. Front. Immunol. 2020, 11, 2156.
  89. Sivori, S.; Vacca, P.; Del Zotto, G.; Munari, E.; Mingari, M.C.; Moretta, L. Human NK cells: Surface receptors, inhibitory checkpoints, and translational applications. Cell Mol. Immunol. 2019, 16, 430–441.
  90. Song, K.; Minami, J.K.; Huang, A.; Dehkordi, S.R.; Lomeli, S.H.; Luebeck, J.; Goodman, M.H.; Moriceau, G.; Krijgsman, O.; Dharanipragada, P.; et al. Plasticity of Extrachromosomal and Intrachromosomal BRAF Amplifications in Overcoming Targeted Therapy Dosage Challenges. Cancer Discov. 2022, 12, 1046–1069.
  91. Chauvin, J.M.; Zarour, H.M. TIGIT in cancer immunotherapy. J. Immunother. Cancer 2020, 8.
  92. Darragh, L.B.; Karam, S.D. Amateur antigen-presenting cells in the tumor microenvironment. Mol. Carcinog. 2022, 61, 153–164.
  93. Verneau, J.; Sautés-Fridman, C.; Sun, C.M. Dendritic cells in the tumor microenvironment: Prognostic and theranostic impact. Semin. Immunol. 2020, 48, 101410.
  94. Ferraro, D.A.; Gaborit, N.; Maron, R.; Cohen-Dvashi, H.; Porat, Z.; Pareja, F.; Lavi, S.; Lindzen, M.; Ben-Chetrit, N.; Sela, M.; et al. Inhibition of triple-negative breast cancer models by combinations of antibodies to EGFR. Proc. Natl. Acad. Sci. USA 2013, 110, 1815–1820.
  95. John, P.; Pulanco, M.C.; Galbo, P.M.; Wei, Y.; Ohaegbulam, K.C.; Zheng, D.; Zang, X. The immune checkpoint B7x expands tumor-infiltrating Tregs and promotes resistance to anti-CTLA-4 therapy. Nat. Commun. 2022, 13, 2506.
  96. Danikowski, K.M.; Jayaraman, S.; Prabhakar, B.S. Regulatory T cells in multiple sclerosis and myasthenia gravis. J. Neuroinflamm. 2017, 14, 117.
  97. Duraiswamy, J.; Kaluza, K.M.; Freeman, G.J.; Coukos, G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res. 2013, 73, 3591–3603.
  98. Koch, E.A.T.; Schaft, N.; Kummer, M.; Berking, C.; Schuler, G.; Hasumi, K.; Dörrie, J.; Schuler-Thurner, B. A One-Armed Phase I Dose Escalation Trial Design: Personalized Vaccination with IKKβ-Matured, RNA-Loaded Dendritic Cells for Metastatic Uveal Melanoma. Front. Immunol. 2022, 13, 785231.
  99. Christodoulou, M.I.; Zaravinos, A. New Clinical Approaches and Emerging Evidence on Immune-Checkpoint Inhibitors as Anti-Cancer Therapeutics: CTLA-4 and PD-1 Pathways and Beyond. Crit. Rev. Immunol. 2019, 39, 379–408.
  100. Ai, L.; Xu, A.; Xu, J. Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond. Adv. Exp. Med. Biol. 2020, 1248, 33–59.
  101. Naidoo, J.; Page, D.B.; Li, B.T.; Connell, L.C.; Schindler, K.; Lacouture, M.E.; Postow, M.A.; Wolchok, J.D. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann. Oncol. 2015, 26, 2375–2391.
  102. Topalian, S.L.; Hodi, F.S.; Brahmer, J.R.; Gettinger, S.N.; Smith, D.C.; McDermott, D.F.; Powderly, J.D.; Carvajal, R.D.; Sosman, J.A.; Atkins, M.B.; et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 2012, 366, 2443–2454.
  103. Bader, J.E.; Voss, K.; Rathmell, J.C. Targeting Metabolism to Improve the Tumor Microenvironment for Cancer Immunotherapy. Mol. Cell. 2020, 78, 1019–1033.
  104. Osipov, A.; Saung, M.T.; Zheng, L.; Murphy, A.G. Small molecule immunomodulation: The tumor microenvironment and overcoming immune escape. J. Immunother. Cancer 2019, 7, 224.
  105. Mahdavi Gorabi, A.; Sadat Ravari, M.; Sanaei, M.J.; Davaran, S.; Kesharwani, P.; Sahebkar, A. Immune checkpoint blockade in melanoma: Advantages, shortcomings and emerging roles of the nanoparticles. Int. Immunopharmacol. 2022, 113, 109300.
  106. Morante, M.; Pandiella, A.; Crespo, P.; Herrero, A. Immune Checkpoint Inhibitors and RAS-ERK Pathway-Targeted Drugs as Combined Therapy for the Treatment of Melanoma. Biomolecules 2022, 12, 1562.
  107. Goldinger, S.M.; Zimmer, L.; Schulz, C.; Ugurel, S.; Hoeller, C.; Kaehler, K.C.; Schadendorf, D.; Hassel, J.C.; Becker, J.; Hauschild, A.; et al. Upstream mitogen-activated protein kinase (MAPK) pathway inhibition: MEK inhibitor followed by a BRAF inhibitor in advanced melanoma patients. Eur. J. Cancer 2014, 50, 406–410.
  108. Kreft, S.; Glutsch, V.; Zaremba, A.; Schummer, P.; Mohr, P.; Grimmelmann, I.; Gutzmer, R.; Meier, F.; Pföhler, C.; Sachse, M.M.; et al. MAPKinase inhibition after failure of immune checkpoint blockade in patients with advanced melanoma - An evaluation of the multicenter prospective skin cancer registry ADOREG. Eur. J. Cancer 2022, 167, 32–41.
  109. Schirmer, M.; Garner, A.; Vlamakis, H.; Xavier, R.J. Microbial genes and pathways in inflammatory bowel disease. Nat. Rev. Microbiol. 2019, 17, 497–511.
  110. Lam, K.C.; Araya, R.E.; Huang, A.; Chen, Q.; Di Modica, M.; Rodrigues, R.R.; Lopès, A.; Johnson, S.B.; Schwarz, B.; Bohrnsen, E.; et al. Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment. Cell 2021, 184, 5338–5356.e5321.
  111. Thomas, S.C.; Madaan, T.; Kamble, N.S.; Siddiqui, N.A.; Pauletti, G.M.; Kotagiri, N. Engineered Bacteria Enhance Immunotherapy and Targeted Therapy through Stromal Remodeling of Tumors. Adv. Healthc. Mater 2022, 11, e2101487.
  112. Fukuhara, H.; Ino, Y.; Todo, T. Oncolytic virus therapy: A new era of cancer treatment at dawn. Cancer Sci. 2016, 107, 1373–1379.
  113. Goradel, N.H.; Baker, A.T.; Arashkia, A.; Ebrahimi, N.; Ghorghanlu, S.; Negahdari, B. Oncolytic virotherapy: Challenges and solutions. Curr. Probl. Cancer 2021, 45, 100639.
  114. Russell, S.J.; Peng, K.W.; Bell, J.C. Oncolytic virotherapy. Nat. Biotechnol. 2012, 30, 658–670.
  115. Gentile, C.; Finizio, A.; Froechlich, G.; D’Alise, A.M.; Cotugno, G.; Amiranda, S.; Nicosia, A.; Scarselli, E.; Zambrano, N.; Sasso, E. Generation of a Retargeted Oncolytic. Int. J. Mol. Sci. 2021, 22, 13521.
  116. Yu, L.; Sun, M.; Zhang, Q.; Zhou, Q.; Wang, Y. Harnessing the immune system by targeting immune checkpoints: Providing new hope for Oncotherapy. Front. Immunol. 2022, 13, 982026.
  117. Gujar, S.A.; Marcato, P.; Pan, D.; Lee, P.W. Reovirus virotherapy overrides tumor antigen presentation evasion and promotes protective antitumor immunity. Mol. Cancer Ther. 2010, 9, 2924–2933.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Naji Kharouf
,
Thomas W. Flanagan
,
Sofie-Yasmin Hassan
,
Hosam Shalaby
,
Marla Khabaz
,
Sarah-Lilly Hassan
,
Mosaad Megahed
,
Youssef Haikel
,
Simeon Santourlidis
,
Mohamed Hassan
View Times: 194
Revisions: 2 times (View History)
Update Date: 25 Jun 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback