德国慕尼黑工业大学Jan P. Böttcher课题组发现，一种独特的刺激性cDC1亚群可扩大肿瘤中的CD8⁺T细胞反应，从而实现保护性抗癌免疫。相关论文于2023年7月13日在线发表在《癌细胞》杂志上。

研究人员使用基于成像的深度学习来识别瘤内1型常规树突状细胞（cDC1）-CD8⁺T细胞簇作为保护性抗癌免疫的一个独特特征。这些簇选择性地形成于基质肿瘤区域，并构成了cDC1激活TCF1⁺干细胞样CD8⁺T细胞的微环境。研究人员发现了一群独特的免疫刺激性CCR7^negcDC1，它们产生CXCL9来促进簇的形成，并在这些微环境中交叉呈递肿瘤抗原，这是肿瘤内CD8⁺T细胞分化和扩增所必需的，并促进了癌症免疫控制。同样，在人类癌症中，CCR7^negcDC1与簇中的CD8⁺T细胞相互作用，并与患者生存有关。

这些发现揭示了肿瘤驻留的cDC1所协调的抗癌T细胞反应的瘤内阶段，它决定了保护性免疫与无效免疫，并可用于癌症治疗。

据悉，cDC1可支持肿瘤内的T细胞应答，但这是否决定了保护性抗癌免疫与无效抗癌免疫之间的关系还不甚明了。

附：英文原文

Title: A distinct stimulatory cDC1 subpopulation amplifies CD8+ T cell responses in tumors for protective anti-cancer immunity

Author: Philippa Meiser, Moritz A. Knolle, Anna Hirschberger, Gustavo P. de Almeida, Felix Bayerl, Sebastian Lacher, Anna-Marie Pedde, Sophie Flommersfeld, Julian Hnninger, Leonhard Stark, Fabian Stgbauer, Martina Anton, Markus Wirth, Dirk Wohlleber, Katja Steiger, Veit R. Buchholz, Barbara Wollenberg, Christina E. Zielinski, Rickmer Braren, Daniel Rueckert, Percy A. Knolle, Georgios Kaissis, Jan P. Bttcher

Issue&Volume: 2023-07-13

Abstract: Type 1 conventional dendritic cells (cDC1) can support T cell responses within tumors but whether this determines protective versus ineffective anti-cancer immunity is poorly understood. Here, we use imaging-based deep learning to identify intratumoral cDC1-CD8+ T cell clustering as a unique feature of protective anti-cancer immunity. These clusters form selectively in stromal tumor regions and constitute niches in which cDC1 activate TCF1+ stem-like CD8+ T cells. We identify a distinct population of immunostimulatory CCR7neg cDC1 that produce CXCL9 to promote cluster formation and cross-present tumor antigens within these niches, which is required for intratumoral CD8+ T cell differentiation and expansion and promotes cancer immune control. Similarly, in human cancers, CCR7neg cDC1 interact with CD8+ T cells in clusters and are associated with patient survival. Our findings reveal an intratumoral phase of the anti-cancer T cell response orchestrated by tumor-residing cDC1 that determines protective versus ineffective immunity and could be exploited for cancer therapy.

DOI: 10.1016/j.ccell.2023.06.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00218-0