美国马萨诸塞州总医院Thorsten R. Mempel研究组报道树突状细胞(DC)在肿瘤中作为T细胞免疫的牧羊人。这一研究成果于近日发表在国际顶尖学术期刊《免疫》上。

他们回顾了目前对DC-T细胞在免疫反应的启动和效应位点的相互作用的理解。他们在DC的发展、个体发生和其他环境下的功能背景下，对DC在肿瘤免疫中的功能进行了新见解，并提出DC控制至少两个癌症免疫周期的T细胞相关检查点。他们对这两个检查点的理解对癌症免疫治疗新方法的发展具有启示意义。

据悉，在癌症患者中，肿瘤引流淋巴结中的DC可以以破坏免疫耐受的方式向幼稚T细胞呈递抗原。引物T细胞的克隆扩增后代进一步受到肿瘤部位DC的调控。瘤内DC既能向传入的T细胞提供生存信号，又能驱动效应分化，从而局部增强抗肿瘤免疫;然而，肿瘤内DC的缺乏或其免疫调节分子的表达往往限制了抗肿瘤T细胞的反应。

附：英文原文

Title: Dendritic cells as shepherds of T cell immunity in cancer

Author: Mikael J. Pittet, Mauro Di Pilato, Christopher Garris, Thorsten R. Mempel

Issue&Volume:

Abstract: In cancer patients, dendritic cells (DCs) in tumor-draining lymph nodes can presentantigens to naive T cells in ways that break immunological tolerance. The clonallyexpanded progeny of primed T cells are further regulated by DCs at tumor sites. IntratumoralDCs can both provide survival signals to and drive effector differentiation of incomingT cells, thereby locally enhancing antitumor immunity; however, the paucity of intratumoralDCs or their expression of immunoregulatory molecules often limits antitumor T cellresponses. Here, we review the current understanding of DC-T cell interactions atboth priming and effector sites of immune responses. We place emerging insights intoDC functions in tumor immunity in the context of DC development, ontogeny, and functionsin other settings and propose that DCs control at least two T cell-associated checkpointsof the cancer immunity cycle. Our understanding of both checkpoints has implicationsfor the development of new approaches to cancer immunotherapy.

DOI: 10.1016/j.immuni.2023.08.014

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00370-9