T细胞在塑造肿瘤微环境中的范式

Dia Roy, S. Bose, S. Dutta, G. Sa
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摘要

免疫细胞在肿瘤微环境中的浸润在癌症患者中得到了充分的证明,由此产生的复杂相互作用是疾病预后的决定因素。因此,正确理解这种相互作用对于治疗策略的发展和进步以及新的预后标志物至关重要。免疫细胞与肿瘤共存通常伴随着免疫反应受损,从而产生促肿瘤的微环境。t细胞介导的免疫形成了免疫系统的主要分支,需要对新生肿瘤进行有效的反应。近几十年来的主要研究表明,在肿瘤部位普遍存在的免疫抑制细胞和分子网络的一个强有力的来源是由T细胞介导的功能失调和缺陷反应介导的,从而重定向和重塑T细胞的命运,促进肿瘤的进展。在这篇综述中,我们旨在总结近年来的突破性进展,以帮助我们更好地理解肿瘤微环境中t细胞能量、衰竭、衰老和Treg细胞的存在所导致的免疫抑制网络。我们还关注最近在Th17平衡、T细胞多功能性以及T细胞干细胞方面的发现,这些发现改善了我们对肿瘤-免疫相互作用的认识。我们试图强调这些信息如何对治疗发展和患者的临床结果产生影响。
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The Paradigm of T Cells in Shaping Tumor Microenvironment
The infiltration of immune cells in the tumor micro-environment is well-documented in cancer patients and the resultant complex interactions are determinants of disease prognosis. Consequently, a proper understanding of this interplay is essential for the development and advancement of therapeutic strategies as well as novel prognostic markers. The co-existence of immune cells with the tumor is often accompanied by an impaired immune response that creates a tumor-promoting micro-environment. T-cell mediated immunity forms the major branch of the immune system that is required to mount an effective response against nascent tumors. Major research in the last few decades indicates that a potent source of immunosuppressive cellular and molecular networks prevailing at the site of tumor is mediated by dysfunctional and defective responses mediated by T cell thereby redirecting and reshaping the destiny of T cell and promoting tumor progression. In this review, we aim to summarize the breakthrough advances in recent years that help us gain a better understanding of the immunosuppressive networks resulting from T-cell anergy, exhaustion, senescence and presence of Treg cells in the tumor micro-environment. We also focus on recent discoveries regarding advance in the Th17 balance, polyfunctionality of T cells as well as T cell stemness that improve our perception of the tumor-immunity interactions. We try to emphasize how such information has an impact on therapeutic development and the clinical outcome of the patients.
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