免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
树突状细胞通过定位 CD8 皮肤驻留记忆 T 细胞来维持抗肿瘤免疫
英文原题：Dendritic cells maintain anti-tumor immunity by positioning CD8 skin-resident memory T cells.
查看英文原题
Dendritic cells maintain anti-tumor immunity by positioning CD8 skin-resident memory T cells.
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中文摘要
组织驻留记忆（T RM）T 细胞正逐渐被认为是抗肿瘤免疫反应的关键组成部分；然而，其持续功能和维持所需的条件仍不清楚。APC 促进 T RM 细胞分化和再激活，但尚未被认为参与维持 T RM 细胞反应。在此，我们发现了树突状细胞在支持针对黑色素瘤的 T RM 中的新作用。我们发现 CD8 T RM 细胞在皮肤中与树突状细胞保持紧密相邻。清除 CD11c+ 细胞会导致黑色素瘤特异性 T RM 细胞迅速解聚并最终丢失。此外，我们确定 T RM 迁移和/或持续存在需要由 CXCR6/CXCL16 轴介导的趋化和黏附。表达 CXCR6 的 T RM 细胞与表达 CXCL16 的 APC 之间的相互作用被发现对于维持 T RM 细胞介导的肿瘤保护至关重要。这些发现大幅拓展了我们对 APC 在 T RM T 细胞稳态和长寿中功能的认识。
展开英文摘要原文
Tissue-resident memory (T RM ) T cells are emerging as critical components of the immune response to cancer; yet, requirements for their ongoing function and maintenance remain unclear. APCs promote T RM cell differentiation and re-activation but have not been implicated in sustaining T RM cell responses.
Here, we identified a novel role for dendritic cells in supporting T RM to melanoma.
We showed that CD8 T RM cells remain in close proximity to dendritic cells in the skin. Depletion of CD11c + cells results in rapid disaggregation and eventual loss of melanoma-specific T RM cells.
In addition, we determined that T RM migration and/or persistence requires chemotaxis and adhesion mediated by the CXCR6/CXCL16 axis. The interaction between CXCR6-expressing T RM cells and CXCL16-expressing APCs was found to be critical for sustaining T RM cell-mediated tumor protection.
These findings substantially expand our knowledge of APC functions in T RM T-cell homeostasis and longevity.
论文信息
- 作者
- Vella JL、Molodtsov A、Angeles CV、Branchini BR、Turk MJ、Huang YH
- 第一作者单位
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.Lebanon
- 通讯作者单位
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA yina.h.huang@dartmouth.edu.Lebanon
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究 · 美国政府（非公共卫生署）资助研究
- 期刊
- Life science alliance2021 Oct
- 原文标识
- PubMed 34362825 · DOI 10.26508/lsa.202101056
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