Tumor-Infiltrating γδ T Lymphocytes: Pathogenic Role, Clinical Significance, and Differential Programing in the Tumor Microenvironment.
Tumor-Infiltrating γδ T Lymphocytes: Pathogenic Role, Clinical Significance, and Differential Programing in the Tumor Microenvironment.
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DOI：
10.3389/fimmu.2014.00607
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发表时间：
2014
影响因子：
7.3
通讯作者：
Meraviglia S
中科院分区：
文献类型：
--
作者：
Lo Presti E;Dieli F;Meraviglia S
越来越多的临床证据表明，免疫系统可能促进或抑制肿瘤的进展。多项研究表明，处于缓解期的肿瘤大量被T淋巴细胞浸润[tumor-浸润淋巴细胞（tumor-浸润淋巴细胞，TILs）]，但另一方面，多项研究表明，肿瘤也可能被具有抑制特征的TILs浸润，这表明TILs与肿瘤进展和不良预后有相当大的关系。γδ T淋巴细胞是TILs的重要组成部分，可能有助于肿瘤免疫监视，一些小型i期临床试验的有希望的报告也表明了这一点。通常，γδ T淋巴细胞在抗肿瘤免疫反应（细胞毒性、IFN-γ和TNF-α的产生以及树突状细胞成熟）中发挥效应功能，但在适当的条件下，它们可能从典型的th1样表型转移到Th2、Th17和Treg细胞，从而获得抑制抗肿瘤免疫反应和促进肿瘤生长的能力。最近的研究表明，γδ T淋巴细胞浸润不同类型的癌症的频率很高，但这种关联的性质及其背后的确切机制仍然不确定，肿瘤浸润γδ T淋巴细胞的存在是否是一个明确的预后因素仍然存在争议。本文将对不同类型肿瘤患者肿瘤浸润性γδ T淋巴细胞的研究进行综述，并讨论其临床意义。此外，我们还将讨论癌症、肿瘤基质和γδ T淋巴细胞之间复杂的相互作用，作为γδ T淋巴细胞应答最终结果的主要决定因素。最后，我们提出靶向γδ T淋巴细胞极化并扭曲其表型以适应微环境可能对癌症的治疗有很大的希望。
There is increasing clinical evidence indicating that the immune system may either promote or inhibit tumor progression. Several studies have demonstrated that tumors undergoing remission are largely infiltrated by T lymphocytes [tumor-infiltrating lymphocytes (TILs)], but on the other hand, several studies have shown that tumors may be infiltrated by TILs endowed with suppressive features, suggesting that TILs are rather associated with tumor progression and unfavorable prognosis. γδ T lymphocytes are an important component of TILs that may contribute to tumor immunosurveillance, as also suggested by promising reports from several small phase-I clinical trials. Typically, γδ T lymphocytes perform effector functions involved in anti-tumor immune responses (cytotoxicity, production of IFN-γ and TNF-α, and dendritic cell maturation), but under appropriate conditions they may divert from the typical Th1-like phenotype and polarize to Th2, Th17, and Treg cells thus acquiring the capability to inhibit anti-tumor immune responses and promote tumor growth. Recent studies have shown a high frequency of γδ T lymphocytes infiltrating different types of cancer, but the nature of this association and the exact mechanisms underlying it remain uncertain and whether or not the presence of tumor-infiltrating γδ T lymphocytes is a definite prognostic factor remains controversial. In this paper, we will review studies of tumor-infiltrating γδ T lymphocytes from patients with different types of cancer, and we will discuss their clinical relevance. Moreover, we will also discuss on the complex interplay between cancer, tumor stroma, and γδ T lymphocytes as a major determinant of the final outcome of the γδ T lymphocyte response. Finally, we propose that targeting γδ T lymphocyte polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of cancer.