Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, NE Glisan St., Portland, OR, 480597213, USA.
Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The OH State University, Columbus, OH, 43210, USA.
Sci Rep. 2023 Apr 18;13(1):6277. doi: 10.1038/s41598-023-33508-1.
Tissue resident memory (Trm) CD8 T cells infiltrating tumors represent an enriched population of tumor antigen-specific T cells, and their presence is associated with improved outcomes in patients. Using genetically engineered mouse pancreatic tumor models we demonstrate that tumor implantation generates a Trm niche that is dependent on direct antigen presentation by cancer cells. However, we observe that initial CCR7-mediated localization of CD8 T cells to tumor draining lymph nodes is required to subsequently generate CD103 CD8 T cells in tumors. We observe that the formation of CD103 CD8 T cells in tumors is dependent on CD40L but independent of CD4 T cells, and using mixed chimeras we show that CD8 T cells can provide their own CD40L to permit CD103 CD8 T cell differentiation. Finally, we show that CD40L is required to provide systemic protection against secondary tumors. These data suggest that CD103 CD8 T cell formation in tumors can occur independent of the two-factor authentication provided by CD4 T cells and highlight CD103 CD8 T cells as a distinct differentiation decision from CD4-dependent central memory.
浸润肿瘤的组织驻留记忆 (Trm) CD8 T 细胞代表了肿瘤抗原特异性 T 细胞的丰富群体,其存在与患者的预后改善相关。使用基因工程小鼠胰腺肿瘤模型,我们证明肿瘤植入产生了依赖于癌细胞直接抗原呈递的 Trm 龛位。然而,我们观察到初始 CCR7 介导的 CD8 T 细胞向肿瘤引流淋巴结的定位对于随后在肿瘤中产生 CD103 CD8 T 细胞是必需的。我们观察到肿瘤中 CD103 CD8 T 细胞的形成依赖于 CD40L,但不依赖于 CD4 T 细胞,并且使用混合嵌合体我们表明 CD8 T 细胞可以提供自己的 CD40L 以允许 CD103 CD8 T 细胞分化。最后,我们表明 CD40L 是提供针对继发性肿瘤的系统保护所必需的。这些数据表明,肿瘤中 CD103 CD8 T 细胞的形成可以独立于 CD4 T 细胞提供的双因素验证发生,并强调 CD103 CD8 T 细胞是与 CD4 依赖性中央记忆不同的分化决定。
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