决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:The Role of Tumour-Infiltrating Lymphocytes in the Immune Microenvironment of Lymphoma and Their Immunotherapeutic Potential.
本综述阐明了TIL在淋巴瘤免疫微环境中的关键作用及其免疫治疗价值。优化TIL培养条件并结合基因编辑和生物工程将提高治疗效果和临床适用性,为淋巴瘤的临床治疗提供新思路。
TIL(肿瘤浸润淋巴细胞)(TILs),包括CD8+ T细胞、CD4+ T细胞、B细胞和NK 细胞,在抗肿瘤免疫应答中发挥关键作用,并通过与肿瘤微环境中的免疫抑制因子交互作用来调节肿瘤免疫逃逸。尽管具有内在的抗肿瘤活性,TIL的功能在很大程度上受到免疫逃逸和细胞耗竭的限制。TILs还与PD-1/PD-L1和CTLA-4协同作用,调节抗肿瘤免疫的强度和持久性,并已成为评估淋巴瘤免疫治疗疗效的有价值生物标志物。
本综述系统总结了近期已发表文献中关于TIL在淋巴瘤中的生物学功能、免疫调节机制及临床研究进展。
TIL在淋巴瘤免疫治疗中展现出有前景的潜力,而基于TIL的策略仍面临细胞制备复杂、疗效不稳定和耐药性的挑战。需要进一步研究以阐明TIL异质性、刻画多样的免疫逃逸机制,并优化临床培养方案。
BACKGROUND: Tumour-infiltrating lymphocytes (TILs), including CD8 + T cells, CD4 + T cells, B cells and natural killer cells, play a key role in anti-tumour immune responses and modulate tumour immune escape via crosstalk with immunosuppressive factors in the tumour microenvironment. Despite inherent anti-tumour activity, TIL function is largely constrained by immune escape and cellular exhaustion. TILs also synergise with PD-1/PD-L1 and CTLA-4 to regulate the magnitude and persistence of anti-tumour immunity, and have emerged as valuable biomarkers for evaluating immunotherapeutic efficacy in lymphoma. METHODS: This review systematically summarises recent published literature regarding the biological function, immune regulatory mechanisms and clinical research progress of TILs in lymphoma. RESULTS: TILs exhibit promising potential in lymphoma immunotherapy, whereas TIL-based strategies remain challenged by complex cell preparation, unstable therapeutic efficacy and drug resistance. Further research is required to clarify TIL heterogeneity, characterise diverse immune escape mechanisms, and optimise clinical culture protocols. CONCLUSIONS: This review clarifies the pivotal role of TILs in the lymphoma immune microenvironment and their immunotherapeutic value. Optimising TIL culture conditions combined with gene editing and bioengineering will improve therapeutic efficacy and clinical applicability, offering novel insights for clinical treatment of lymphoma.
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