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Effective anti-tumor immunity is largely driven by cytotoxic CD8 T cells that can specifically recognize tumor antigens. However, the factors which ultimately dictate successful tumor rejection remain poorly understood. Here we identify a subpopulation of CD8 T cells which are tumor antigen-specific in patients with melanoma but resemble KIRCD8 T cells with a regulatory function (Tregs). These tumor antigen-specific KIRCD8 T cells are detectable in both the tumor and the blood, and higher levels of this population are associated with worse overall survival. Our findings therefore suggest that KIRCD8 Tregs are tumor antigen-specific but uniquely suppress anti-tumor immunity in patients with melanoma.
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http://dx.doi.org/10.21203/rs.3.rs-3956671/v1 | DOI Listing |
EMBO J
September 2025
Department of Infectious Diseases, Medical Research Institute, Zhongnan Hospital of Wuhan University; Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences; Wuhan University, Wuhan, 430071, China.
Inadequate antigen presentation by MHC-I in tumor microenvironment (TME) is a common immune escape mechanism. Here, we show that glycine decarboxylase (GLDC), a key enzyme in glycine metabolism, functions as an inhibitor of MHC-I expression in EGFR-activated tumor cells to induce immune escape by a mechanism independent of its enzymatic activity. Upon EGFR activation, GLDC is phosphorylated by SRC and subsequently translocated to the nucleus in human NSCLC cells.
View Article and Find Full Text PDFCell Mol Immunol
September 2025
Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China.
Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD) is hampered by issues of nonresponse and resistance, highlighting the urgent need for alternative or complementary treatments. Our study revealed significant upregulation of taurine in the intestinal tissues of IBD patients, which was inversely related to the severity of the disease. A key discovery was that TNF directly induced taurine synthesis in intestinal epithelial cells and increased the production of angiogenin, a nuclease that degrades mitochondrial RNA, which is known to amplify inflammatory responses.
View Article and Find Full Text PDFCancer Lett
September 2025
State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Department of Radiology, Department of Clinical Research and Translational Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou,
The tumor microenvironment (TME) plays a pivotal role in cancer progression, though the molecular regulators governing its immunosuppressive properties remain incompletely characterized. In this study, we identify Makorin-2 (MKRN2) as a novel modulator of TME remodeling through integrated analyses of genetically engineered mouse models and human clinical data. Utilizing MKRN2 knockout mice, we observed significantly accelerated tumor growth compared to wild-type control, which was associated with profound alterations in immune cell composition, especially M2 macrophages.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Department of Chemical & Biochemical Engineering, Dongguk University, Seoul, 04620, Republic of Korea. Electronic address:
Modified hyaluronic acid (HA) biomaterials have received considerable attention in recent years, especially in developing innovative therapeutic strategies for targeted disease interventions. HA serves to shield therapeutics from the physiological environment, while enabling safe delivery and promoting uptake into specific cells. As a hydrophilic chain polymer, HA is readily chemically modified into functional biomaterials for drug delivery and cancer immunotherapy.
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.
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