美国圣路易斯华盛顿大学Eynav Klechevsky小组发现，树突状细胞的CD5表达指导T细胞免疫并维持免疫治疗反应。这一研究成果发表在2023年2月17日出版的国际学术期刊《科学》上。

研究人员发现，人CD1c⁺CD5⁺树突状细胞（DC）在黑色素瘤感染的淋巴结中减少，树突状细胞中CD5表达与患者生存率相关。在DC上激活CD5增强了T细胞启动，并提高了免疫检查点阻断（ICB）治疗后的生存率。在ICB治疗期间，CD5⁺DC数量增加，低白介素-6（IL-6）浓度促进了它们的新生分化。机制上，DC表达CD5是产生最佳保护性CD5^hi辅助T细胞和CD8⁺T细胞所需的；此外，在体内，T细胞中CD5的缺失抑制了ICB治疗对肿瘤的消除。因此，CD5⁺DC是最佳ICB治疗的重要组成部分。

据悉，DC亚型诱导促炎T细胞对于抗肿瘤反应和有效的ICB治疗至关重要。

附：英文原文

Title: CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses

Author: Mingyu He, Kate Roussak, Feiyang Ma, Nicholas Borcherding, Vince Garin, Mike White, Charles Schutt, Trine I. Jensen, Yun Zhao, Courtney A. Iberg, Kairav Shah, Himanshi Bhatia, Daniel Korenfeld, Sabrina Dinkel, Judah Gray, Alina Ulezko Antonova, Stephen Ferris, David Donermeyer, Cecilia Lindestam Arlehamn, Matthew M. Gubin, Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus Bak, Robert L. Modlin, Ryan C. Fields, Robert D. Schreiber, Paul M. Allen, Eynav Klechevsky

Issue&Volume: 2023-02-17

Abstract: The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c+CD5+ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5+ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Thus, CD5+ DCs are an essential component of optimal ICB therapy.

DOI: abg2752

Source: https://www.science.org/doi/10.1126/science.abg2752