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Immunotherapy in Solid Tumors

Immunotherapy has emerged as a major therapeutic modality in oncology. The number of immunotherapy drug approvals has been increasing, with numerous treatments in clinical and preclinical development. These therapeutics help the host immune system recognize cancer as foreign, promote the immune system, and relieve the inhibition that allows growth and spread of tumors.

 

Despite advancements in the treatment of hematological malignancies, solid tumors still represent a challenge. The majority of patients with cancer do not derive benefit from these treatments. Vascular abnormalities are a hallmark of most solid tumors and facilitate immune evasion. These underscore the importance of understanding basic tumor immunology for successful clinical translation in treating patients with cancer.

The recent clinical successes of immune checkpoint blockade therapies represent a turning point in immunotherapy. In addition, other immunotherapeutic treatments, such as vaccines, antibody-based targeted therapies, and adoptive therapies, are being investigated to treat solid tumors.

This entries collection intends to present insights into the novel approaches in immunotherapy and discuss existing and emerging immunotherapy technologies that hope to translate the promise of immunotherapy for the treatment of solid tumors into clinical reality.

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Topic review
Updated time: 28 Jul 2021
Definition: Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging (MRI), serum and cerebrospinal fluid (CSF) markers, and tumour stereotactic biopsy. Imaging techniques, such as susceptibility-weighted imaging (SWI), T2* (T2-star) gradient echo (GRE) or arterial spin labelling based perfusion-weighted MRI (ASL-PWI) facilitate the diagnosis.
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Topic review
Updated time: 06 Sep 2021
Submitted by: Susumu Hijioka
Definition: Endoscopic ultrasonography (EUS) has greater spatial resolution than other diagnostic imaging modalities. In addition, if gallbladder lesions are found and gallbladder cancer is suspected, EUS is an indispensable modality, enabling detailed tests for invasion depth evaluation using the Doppler mode and ultrasound agents. Furthermore, for gallbladder lesions, EUS fine-needle aspiration (EUS-FNA) can be used to differentiate benign and malignant forms of conditions, such as xanthogranulomatous cholecystitis, and collect evidence before chemotherapy.
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Biography
Updated time: 19 Jul 2021
Submitted by: Christine Jean
Abstract: Solid cancer progression is dictated by neoplastic cell features and pro-tumoral crosstalks with their microenvironment. Stroma modifications, such as fibroblast activation into cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) remodeling, are now recognized as critical events for cancer progression and as potential therapeutic or diagnostic targets.
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Topic review
Updated time: 30 Jul 2021
Submitted by: Gabriella De Vita
Definition: Forkhead box E1 (FOXE1) is a transcription factor involved in thyroid cancer susceptibility. Here we show that FOXE1 expression in thyroid cells correlate with chemokines induction and monocyte chemoattraction, and that reduction of FOXE1 gene dosage in vivo impairs macrophage infiltration in thyroid cancer.
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Topic review
Updated time: 17 Sep 2021
Submitted by: Pierre-Simon Bellaye
Definition: Tumors are not only composed of cancer cells but also of various infiltrating cells constituting the tumor microenvironment (TME); all these cells produce growth factors which contribute to tumor progression and invasiveness. Among them, TGF-β, in particular the predominant isoform, TGF-β1, plays a major role in tumor progression due to its pleiotropic effects (1). TGF-β is, in fact, a potent immunosuppressive cytokine, impacting antitumor immune responses (2) and it has many other protumor effects related to its role in epithelial–mesenchymal transition, cell proliferation, cell invasion and angiogenesis (3,4) and resistance to treatments (5,6). However, its use as a biomarker is made difficult by the existence of several inactive forms upstream of the biologically active TGF-β. Glycoprotein-A repetition predominant (GARP) is the docking receptor for latent transforming growth factor (LTGF-β) and promotes its activation. Increased GARP expression has been found in many types of cancer. GARP is expressed by regulatory T cells and platelets in the tumor microenvironment (TME) and can be also expressed by tumor cells themselves. Thus, GARP can be widely present in tumors in which it plays a major role in the production of active TGF-β, contributing to immune evasion and cancer progression via the GARP-TGF-β axis. The objective of this review is to highlight GARP’s expression and function in cancer and to evaluate its potential as a predictive and therapeutic follow-up biomarker that could be assessed, in real time, by molecular imaging.
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Topic review
Updated time: 02 Jul 2021
Submitted by: Srikanth Umakanthan
Definition: Global genomic studies have detected the role of genomic alterations in the pathogenesis of Epstein–Barr virus (EBV)-associated tumors. EBV oncoproteins cause a vital shift of EBV from an infectious virus to an oncogenic form during the latent and lytic phase within the lymphoid B cells and epithelial cells. This epigenetic alteration modulates the virus and host genomes and inactivates and disrupts numerous tumor suppressors and signaling pathways. Genomic profiling has played the main role in identifying EBV cancer pathogenesis and its related targeted therapies.
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Topic review
Updated time: 11 Aug 2021
Submitted by: Maria Caffarel
Definition: Epithelial–mesenchymal plasticity (EMP) plays critical physiological roles during embryonic development, postnatal growth and epithelial homeostasis, but it is also involved in a number of pathological conditions, including wound repair, fibrosis, inflammation and cancer. EMP has been intimately linked with most, if not all, of the steps during cancer development and progression (e.g., migration, invasion, immune escape, drug resistance and metastatic dissemination). Cytokines from the interleukin 6 (IL-6) family play fundamental roles in mediating tumour-promoting inflammation within the tumour microenvironment. In general, IL-6 cytokines activate EMP processes, fostering the acquisition of mesenchymal features in cancer cells. Here, we will summarise all the relevant literature related to all members of the IL-6 family and EMP.
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Topic review
Updated time: 27 Oct 2021
Submitted by: Shih-Hsuan Chan
Definition: Hepatocellular carcinoma is the most prevalent form of liver cancer in the world. Annually, HCC affects approximately 900,000 individuals, and over 70% of new cases are diagnosed in Asia. The etiology of HCC is complicated due to the multiple risk factors involved.
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Topic review
Updated time: 17 Nov 2021
Submitted by: Marcus Schmidt
Definition: Review of the role of the immune system in breast cancer. It covers the prognostic and predictive impact of tumor-infiltrating lymphocytes. Furthermore therapeutic advances ranging from immune checkpoint inhibitors and personalized vaccination strategies are highlighted.
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Topic review
Updated time: 27 Oct 2021
Submitted by: Giulia Martini
Definition: The combination of immune checkpoint inhibitors with target agents has been explored in hepatocellular carcinoma. The combination of an immunecheckpoint inhibitor with an anti-angiogenic drug has proved effectiveness as per the case of the IMBRAVE150 trial of atezolizumab plus bevacizumab mentioned above. Furthermore, novel immunotherapy and target agents combinations are currently being explored in first-line settings in different clinical trials to better define novel treatment opportunities for patients with HCC.
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