γδ T 细胞调节小细胞肺癌中的抗肿瘤免疫
γδ T cells modulate anti-tumor immunity in small cell lung cancer.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Local γδ T cells: translating promise to practice in cancer immunotherapy.
Local γδ T cells: translating promise to practice in cancer immunotherapy.
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过去十年,基础免疫学向癌症免疫治疗的快速 bench-to-bedside 转化彻底改变了肿瘤学的临床实践。靶向 αβ T 细胞的免疫检查点抑制剂如今为部分既往治疗难治性转移性癌症患者提供了持久缓解甚至治愈。遗憾的是,这些治疗仅使少数患者获益,而通过利用 αβ T 细胞的联合治疗提高疗效的努力已出现收益递减。与 αβ T 细胞和 B 细胞并列,γδ T 细胞是适应性淋巴细胞的第三谱系。人们对这些细胞了解较少,且它们在癌症免疫治疗中仍相对未经充分检验。尽管临床前证据支持其应用价值,但涉及 γδ T 细胞的少数早期试验未能在实体癌中证明令人信服的疗效。
在此,我们综述了关于这些细胞如何被调控,尤其是组织局部调控的最新认识进展及其转化潜力。我们特别关注 butyrophilin (BTN) 和 BTN-like (BTNL) 调控 γδ T 细胞领域的最新进展,并推测这些进展如何可能解决既往利用这些细胞方法的局限性,以及它们如何可能为将这些细胞用于癌症免疫治疗的新策略提供启示。
Rapid bench-to-bedside translation of basic immunology to cancer immunotherapy has revolutionised the clinical practice of oncology over the last decade. Immune checkpoint inhibitors targeting αβ T cells now offer durable remissions and even cures for some patients with hitherto treatment-refractory metastatic cancers. Unfortunately, these treatments only benefit a minority of patients and efforts to improve efficacy through combination therapies utilising αβ T cells have seen diminishing returns.
Alongside αβ T cells and B cells, γδ T cells are a third lineage of adaptive lymphocytes. Less is known about these cells, and they remain relatively untested in cancer immunotherapy. Whilst preclinical evidence supports their utility, the few early-phase trials involving γδ T cells have failed to demonstrate convincing efficacy in solid cancers.
Here we review recent progress in our understanding of how these cells are regulated, especially locally within tissues, and the potential for translation. In particular, we focus on the latest advances in the field of butyrophilin (BTN) and BTN-like (BTNL) regulation of γδ T cells and speculate on how these advances may address the limitations of historical approaches in utilising these cells, as well as how they may inform novel approaches in deploying these cells for cancer immunotherapy.
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