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Topic Review
Tumor Microenvironment in melanoma
Antitumor therapies have made great strides in recent decades. Chemotherapy, aggressive and unable to discriminate cancer from healthy cells, has given way to personalized treatments that, recognizing and blocking specific molecular targets, have paved the way for targeted and effective therapies. Melanoma was one of the first tumor types to benefit from this new care frontier by introducing specific inhibitors for v-Raf murine sarcoma viral oncogene homolog B (BRAF), mitogen-activated protein kinase (MEK), v-kit Hardy–Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and, recently, immunotherapy. However, despite the progress made in the melanoma treatment, primary and/or acquired drug resistance remains an unresolved problem. The molecular dynamics that promote this phenomenon are very complex but several studies have shown that the tumor microenvironment (TME) plays, certainly, a key role. In this review, we will describe the new melanoma treatment approaches and we will analyze the mechanisms by which TME promotes resistance to targeted therapy and immunotherapy.
  • 1.0K
  • 21 Oct 2020
Topic Review
Tumor Microenvironment in Hepatocellular Carcinoma
The interaction of the cellular environment surrounding the tumor plays a relevant role in hepatocellular carcinoma (HCC) pathogenesis. The tumor microenvironment is directly implicated in the modulation of liver fibrosis, the process of hepatocarcinogenesis, the epithelial-mesenchymal transition (EMT), invasion, and metastasis. Besides liver cancer cells, several cell types participate in the tumor progression in the liver. 
  • 570
  • 25 Feb 2022
Topic Review
Tumor Microenvironment in Glioblastoma Niches
Among gliomas, malignant gliomas and more specifically glioblastomas (GBM) are a challenge in their diagnosis and treatment. Monocytes have been proved to actively participate in tumor growth, giving rise to the support of tumor-associated macrophages (TAMs). In GBM, TAMs represent up to one-half of the tumor mass cells, including both infiltrating macrophages and resident brain microglia. Infiltrating macrophages/monocytes constituted ~ 85% of the total TAM population, they have immune functions, and they can release a wide array of growth factors and cytokines in response to those factors produced by tumor and non-tumor cells from the tumor microenvironment (TME). This cell population has been increasingly studied in GBM TME to understand its role in tumor progression and therapeutic resistance. 
  • 239
  • 07 Apr 2023
Topic Review
Tumor Microenvironment in Glial Neoplasm
Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence.
  • 364
  • 20 Apr 2022
Topic Review
Tumor Microenvironment in Follicular Lymphoma
In the follicular lymphoma (FL) microenvironment, CXCR5+ICOS+PD1+BCL6+ T follicular helper (Tfh) cells, which closely correlate with FL B cells in neoplastic follicles, play a major role in supporting FL. Interleukin-4 secreted by Tfh cells triggers the upregulation of the lymphocyte chemoattractant CXCL12 in stromal cell precursors, in particular by fibroblastic reticular cells (FRCs). 
  • 355
  • 19 Jul 2021
Topic Review
Tumor Microenvironment in Cancer Metastasis
Metastasis, the process by which cancer cells escape primary tumor site and colonize distant organs, is responsible for most cancer-related deaths. The tumor microenvironment (TME), comprises different cell types, including immune cells and cancer-associated fibroblasts, as well as structural elements, such as collagen and hyaluronan that constitute the extracellular matrix (ECM). 
  • 569
  • 08 May 2021
Topic Review
Tumor Microenvironment in Basal and Squamous Cell Carcinoma
It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively.
  • 404
  • 11 May 2023
Topic Review
Tumor Microenvironment in Adrenocortical Carcinoma
Adrenocortical carcinoma is a rare but aggressive malignancy with poor outcomes even for patients with early-stage disease. Several immunotherapy clinical trials, many of which are still in progress, have yielded modest results so far. In-depth understanding of the tumor microenvironment in other cancer types has helped the scientific community to identify novel therapeutic targets and gain a better insight of cancer biology. 
  • 414
  • 30 Apr 2021
Topic Review
Tumor Microenvironment Impact on Follicular Lymphomas
Follicular lymphomas (FL) are neoplasms that resemble normal germinal center (GC) B-cells. Normal GC and neoplastic follicles contain non-neoplastic cells such as T-cells, follicular dendritic cells, cancer associated fibroblasts, and macrophages, which define the tumor microenvironment (TME), which itself is an essential factor in tumor cell survival. The main characteristics of the TME in FL are an increased number of follicular regulatory T-cells (Treg) and follicular helper T-cells (Tfh), M2-polarization of macrophages, and the development of a nodular network by stromal cells that creates a suitable niche for tumor growth. All of them play important roles in tumor angiogenesis, inhibition of apoptosis, and immune evasion, which are key factors in tumor progression and transformation risk. 
  • 254
  • 18 May 2022
Topic Review
Tumor Microenvironment and Metabolism
There is a growing appreciation that the cells of the tumor microenvironment interact via variations in their dynamic regulation of mitochondrial function. The melatonergic pathway is a core aspect of mitochondrial function, with tumors 'domineering' the homeostasis established in the tumor microenvironment by regulating the core functioning of other cells. This is predominantly achieved by regulating the levels of melatonin and its immediate precursor, N-acetylserotonin (NAS). Applying melatonin to any tumor drives tumor death via apoptosis, whilst NAS can activate the trophic receptor, TrkB, to increase the survival and proliferation of tumors. Given such contrasting effects of melatonin and NAS, it is crucial for tumors to regulate the NAS/melatonin ratio within the tumor microenvironment. Two immune cells can readily kill cancer cells, namely natural killer (NK) cells and CD8+ t cells. The tumor inactivates these cells by releasing kynurenine, which activates the aryl hydrocarbon receptor (AhR) on these immune cells, leading to their inactivation ('exhaustion'), with AhR activation also increasing the NAS/melatonin ratio. NAS release enhances the survival and proliferation of cancer stem-like cells, thereby driving tumor maintenance and spread (metastasis). The cells that can readily kill cancer cells are therefore turned into providers of support for tumor survival and spread. This is achieved via the tumor's regulation of the mitochondrial melatonergic pathway. Similar tumor interactions with the mitochondrial melatonergic pathway allows the tumor to regulate other cells in the tumor microenvironment, as well as influencing how these cells interact with each other. This is predominantly achieved by the altered metabolism and mitochondrial function in the tumor shaping the mitochondrial function of other cells in the tumor microenvironment. As mitochondria evolved over evolution from ancient bacteria, these interactions across cell types in the tumor microenvironment may be viewed as evolutionary modified bacteria dynamically interacting with each other within a quest to achieve 'dominance' via the regulation of mitochondrial melatonergic pathway. This is a novel conceptualization of the tumor microenvironment that emphasizes core metabolic processes, and their regulation by the melatonergic pathway. As a frame of reference this allows the incorporation of previously disparate pieces of data on the tumor microenvironment and also provides a clearer pathway to new research, coupled to treatment implications. 
  • 538
  • 05 Jan 2023
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