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Cell重磅:发现肿瘤“破防区”,T细胞由此进入,促进免疫治疗成功
生物世界· 2025-10-20 04:05
Core Viewpoint - The study identifies CRATER (Cancer regions of antigen presentation and T cell engagement and retention) as critical areas on tumor surfaces that facilitate CD8+ T cell engagement, which is essential for the success of immunotherapy [4][10][11]. Group 1: Key Findings - CRATER regions are described as "hotspots" where CD8+ T cells interact with tumor cells, significantly enhancing immune response [8][10]. - The research utilized live imaging techniques in zebrafish to observe that CD8+ T cells gather in specific depressed areas at the edges of melanoma, indicating targeted engagement rather than random movement [9][10]. - CRATER regions are characterized by a diameter of approximately 20-50 micrometers and are rich in antigen-presenting molecules, which are crucial for T cell activation [11][14]. Group 2: Mechanism of Action - CRATER is an active platform that enhances anti-tumor immune responses, with tumor cells expressing higher levels of antigen-presenting molecules (e.g., MHC-I) within these regions [14]. - The expansion of CRATER during immune stimulation correlates with increased accumulation of activated CD8+ T cells, marking it as a primary site for tumor cell apoptosis [14]. Group 3: Clinical Implications - The density of CRATER regions in melanoma patients correlates with the response to immune checkpoint blockade (ICB) therapy, suggesting its potential as a predictive biomarker [16]. - Patients who responded to treatment exhibited significantly higher CRATER density in post-operative biopsy samples compared to non-responders [16]. Group 4: Future Directions - The presence of CRATER has been observed in non-small cell lung cancer, indicating its potential relevance across various solid tumors [18]. - The findings may lead to the development of personalized treatment strategies, where CRATER density could guide predictions of patient responses to immunotherapy [18].