γδT Cells in Tumor Microenvironment
γδT Cells in Tumor Microenvironment
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DOI：
10.1007/978-3-030-49270-0_5
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发表时间：
2020-01-01
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影响因子：
--
通讯作者：
Olive, Daniel
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文献类型：
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作者：
Imbert, Caroline;Olive, Daniel
结合了先天和适应性潜力的伽马德尔塔 (gamma delta) T 细胞具有非凡的特性。事实上，它们强大的细胞毒性和促炎活性使它们能够杀死多种肿瘤细胞。多项研究表明，γδT 细胞是不同类型癌症患者肿瘤浸润淋巴细胞的重要组成部分。在许多研究中，肿瘤浸润性 γδT 细胞也被认为是良好的预后标志物，尽管这些细胞的存在与乳腺癌和结肠癌的不良预后相关。肿瘤微环境似乎驱动γδT细胞向肿瘤促进或肿瘤控制表型分化，这表明某些肿瘤微环境可以限制γδT细胞的有效性。人类中主要的γδT细胞亚群是由磷酸抗原特异性激活的Vγ9Vδ2T细胞。这种独特的抗原激活过程在需要表达嗜丁蛋白 3A (BTN3A) 分子的框架中发挥作用。有趣的是，有一些证据表明 BTN3A 表达可能受到肿瘤微环境的调节。鉴于其强大的抗肿瘤潜力，V gamma 9V delta 2 T细胞可通过离体培养和扩增，然后过继转移给患者或通过直接刺激在体内繁殖来用于治疗方法。这些策略已显示出有希望的初步结果，但还需要更大的效力。将V gamma 9V delta 2 T细胞免疫治疗与恢复肿瘤微环境中的抗肿瘤免疫反应的系统方法相结合可能会提高疗效。在本章中，我们首先回顾了gamma delta T细胞的基本特征及其在肿瘤微环境中的作用，然后分析了这些细胞在肿瘤中激活的理解进展以及为什么这对治疗提出了独特的挑战，最后我们讨论了基于gamma delta T细胞的治疗策略及其未来发展前景。
Gamma delta (gamma delta) T cells which combine both innate and adaptive potential have extraordinary properties. Indeed, their strong cytotoxic and pro-inflammatory activity allows them to kill a broad range of tumor cells. Several studies have demonstrated that gamma delta T cells are an important component of tumor-infiltrated lymphocytes in patients affected by different types of cancer. Tumor-infiltrating gamma delta T cells are also considered as a good prognostic marker in many studies, though the presence of these cells is associated with poor prognosis in breast and colon cancers. The tumor microenvironment seems to drive gamma delta T-cell differentiation toward a tumor-promoting or a tumor-controlling phenotype, which suggests that some tumor microenvironments can limit the effectiveness of gamma delta T cells.The major gamma delta T-cell subsets in human are the V gamma 9V delta 2 T cells that are specifically activated by phosphoantigens. This unique anti-genic activation process operates in a framework that requires the expression of butyrophilin 3A (BTN3A) molecules. Interestingly, there is some evidence that BTN3A expression may be regulated by the tumor microenvironment. Given their strong antitumoral potential, V gamma 9V delta 2 T cells are used in therapeutic approaches either by ex vivo culture and amplification, and then adoptive transfer to patients or by direct stimulation to propagate in vivo. These strategies have demonstrated promising initial results, but greater potency is needed. Combining V gamma 9V delta 2 T-cell immunotherapy with systemic approaches to restore antitumor immune response in tumor microenvironment may improve efficacy.In this chapter, we first review the basic features of gamma delta T cells and their roles in the tumor microenvironment and then analyze the advances about the understanding of these cells' activation in tumors and why this represent unique challenges for therapeutics, and finally we discuss gamma delta T-cell-based therapeutic strategies and future perspectives of their development.