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Immune checkpoint blockade (ICB) has emerged as a novel therapeutic tool for cancer therapy in the last decade. Unfortunately, a small number of patients benefit from approved immune checkpoint inhibitors (ICIs). Therefore, multiple studies are being conducted to find new ICIs and combination strategies to improve the current ICIs. In this review, we discuss some approved immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and also highlight newer emerging ICIs. For instance, HLA-E, overexpressed by tumor cells, represents an immune-suppressive feature by binding CD94/NKG2A, on NK and T cells. NKG2A blockade recruits CD8+ T cells and activates NK cells to decrease the tumor burden. NKG2D acts as an NK cell activating receptor that can also be a potential ICI. The adenosine A2A and A2B receptors, CD47-SIRPα, TIM-3, LAG-3, TIGIT, and VISTA are targets that also contribute to cancer immunoresistance and have been considered for clinical trials. Their antitumor immunosuppressive functions can be used to develop blocking antibodies. PARPs, mARTs, and B7-H3 are also other potential targets for immunosuppression. Additionally, miRNA, mRNA, and CRISPR-Cas9-mediated immunotherapeutic approaches are being investigated with great interest. Pre-clinical and clinical studies project these targets as potential immunotherapeutic candidates in different cancer types for their robust antitumor modulation.
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http://dx.doi.org/10.3390/biology12020218 | DOI Listing |
Esophagus
September 2025
Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, Japan.
Background: The cluster of differentiation 47 (CD47)-signal regulatory protein alpha (SIRPα) axis is a key regulator of innate immune surveillance, facilitating the neoplastic evasion of macrophage-mediated phagocytosis. Although this pathway has been implicated in tumor immune escape in multiple malignancies, its clinical and prognostic significance in esophageal squamous cell carcinoma (ESCC) remain to be fully elucidated.
Methods: We retrospectively analyzed 100 patients who underwent esophagectomy for resectable ESCC.
Zhonghua Jie He He Hu Xi Za Zhi
September 2025
Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Immune-related adverse events (irAE) are treatment-associated complications that single or multiple systems could be involved after immune checkpoint inhibitors(ICI), ranging from mild to life-threatening diseases, with significant heterogeneity. This is an important factor which might affect continuous ICI treatment. Patients who have experienced mild to moderate irAE could try ICI rechallenge after they recovered from irAE.
View Article and Find Full Text PDFCell Rep Med
September 2025
Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. Electronic address:
The success of immune checkpoint inhibitors is limited by multiple factors, including poor T cell infiltration and function within tumors, partly due to a dense extracellular matrix (ECM). Here, we investigate modulating the ECM by targeting integrin α5β1, a major fibronectin-binding and organizing integrin, to improve immunotherapy outcomes. Use of a function-blocking murinized α5β1 antibody reduces fibronectin fibril formation, enhances CD8 T cell transendothelial migration, increases vascular permeability, and decreases vessel-associated collagen.
View Article and Find Full Text PDFPathol Res Pract
September 2025
Department of Biotechnology, Delhi Technological University, India. Electronic address:
The intricate interplay between cancer and autoimmune diseases (ADs) is rooted in immune dysregulation, where genetic susceptibility, chronic inflammation, epigenetic modifications, and immunosuppressive therapies contribute to tumorigenesis. The dualistic nature of immune activation complicates therapeutic strategies, as immune checkpoint inhibitors and other immune-stimulatory therapies may exacerbate underlying ADs, leading to immune-related adverse events (irAEs), including organ toxicity, dermatologic reactions, and disease flares. Conversely, immunosuppressive treatments aimed at controlling ADs can compromise anti-tumor immunity and reduce the efficacy of cancer therapies.
View Article and Find Full Text PDFPurpose: In Armenia, a lower-middle-income country, cancer causes 21% of all deaths, with over half of cases diagnosed at advanced stages. Without universal health insurance, patients rely on out-of-pocket payments or black-market channels for costly immunotherapies, underscoring the need for real-world data to inform equitable policy reforms.
Methods: We conducted a multicenter, retrospective cohort study of patients who received at least one dose of an immune checkpoint inhibitor (ICI) between January 2017 and December 2023 across six Armenian oncology centers.