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Nature Cancer:揭开CAR-T、CAR-NK细胞持久性调控新通路
生物世界· 2025-07-23 08:07
Core Viewpoint - CAR-T cell therapy has significantly transformed the treatment of B-cell malignancies and is showing initial effectiveness in solid tumors, but there is an urgent need to optimize current treatment protocols due to many patients not responding or developing resistance [2]. Group 1: CAR Therapy Mechanisms - The progression of disease after CAR therapy can be attributed to various factors, categorized into intrinsic tumor factors, tumor microenvironment, or intrinsic resistance mechanisms of lymphocytes [2]. - Factors related to lymphocytes expressing CAR are particularly noteworthy, as they may be altered during the in vitro cell manufacturing process [2]. - Recent clinical data indicate that the expansion and persistence of CAR-T cells in vivo are often associated with better therapeutic outcomes, which also applies to CAR-NK cells [2]. Group 2: Research Findings - A study published on July 22, 2025, in Nature Cancer reveals that the persistence of CAR-engineered lymphocytes (CAR-T and CAR-NK cells) is regulated by a FAS ligand–FAS autoregulatory circuit [3][4]. - The expression of FAS ligand (FAS-L) is primarily found in endogenous T cells, natural killer (NK) cells, and CAR-T cells, with minimal expression in tumor and stromal cells [9]. - The research team demonstrated that CAR-T and CAR-NK cell survival is influenced by FAS-L regulation, as evidenced by the enrichment of CAR-T and CAR-NK cells expressing a dominant negative FAS receptor (ΔFAS) post-transplantation [10]. Group 3: Implications for Treatment - The study suggests that the persistence of CAR-engineered lymphocytes is controlled by the FAS-L/FAS autoregulatory circuit, which could have significant implications for enhancing the efficacy of CAR therapies [11].