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.
我们的发现表明,活化的γδ T细胞可能是SCLC治疗的有价值靶点。
英文原题:Gamma Delta T Cells in the Tumour Microenvironment: A Double-Edged Sword.
γδ T细胞代表一类独特的淋巴细胞,能够在肿瘤微环境(TME)内发挥促肿瘤和抗肿瘤的双重功能。
γδ T 细胞代表一类独特的淋巴细胞,能够在肿瘤微环境(TME)内同时发挥促肿瘤和抗肿瘤功能。其独特的能力在于不依赖 MHC 识别应激诱导抗原,从而实现快速免疫监视,使其在癌症免疫监视中成为一把双刃剑。本综述批判性地研究这一二分性,分析其强大的肿瘤抑制作用,这主要由 Vγ9Vδ2 T 细胞等亚群通过穿孔素和颗粒酶释放等细胞毒性机制以及分泌干扰素-γ(IFN-γ)等促炎细胞因子驱动。相反,我们探讨其促肿瘤功能,其中产生 IL-17 的 Vδ1 T 细胞等亚群可促进免疫抑制环境、血管生成和免疫逃逸。本文广泛审视 γδ T 细胞的功能,强调 TME 如何关键性地决定这种功能极化。这种双重性既为癌症免疫治疗带来重大挑战,也提供了有前景的机遇。本文讨论了未来的研究和新出现的治疗策略,包括使用 CAR-γδ T 细胞的过继细胞疗法以及与免疫检查点抑制剂的联合方案,这些策略旨在克服 TME 的抑制屏障。更深入地理解调控 γδ T 细胞功能的分子开关,对于设计能够充分发挥其抗癌潜力的有效下一代疗法至关重要。
Gamma delta (γδ) T cells represent a distinct group of lymphocytes capable of functioning in both pro-tumorigenic and anti-tumorigenic capacities inside the tumour microenvironment (TME). Their unique ability for MHC-independent recognition of stress-induced antigens enables swift immunosurveillance, positioning them as a double-edged sword in cancer immunosurveillance. This review critically investigates this dichotomy, analysing their potent tumour-suppressive roles, which are primarily driven by subsets like Vγ9Vδ2 T cells through cytotoxic mechanisms such as perforin and granzyme release and the secretion of pro-inflammatory cytokines like interferon-gamma (IFN-γ). Conversely, we explore their tumour-promoting functions, wherein subsets such as IL-17-producing Vδ1 T cells can foster an immunosuppressive milieu, angiogenesis, and immune evasion. The function of γδ T cells is extensively examined, emphasising how the TME critically dictates this functional polarisation. This duality presents both a significant challenge and a promising opportunity for cancer immunotherapy. Future investigations and emerging therapeutic strategies are discussed, including the use of adoptive cell therapies with CAR-γδ T cells and combination approaches with immune checkpoint inhibitors, which aim to overcome the TME's suppressive barriers. A deeper understanding of the molecular switches that govern γδ T cell function is paramount for devising effective next-generation therapies that can exploit their full anti-cancer potential.
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