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肿瘤驻留记忆 CD8 T 细胞和伴随的肿瘤免疫的形成独立于 CD4 帮助。

Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help.

机构信息

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.

出版信息

Sci Rep. 2023 Apr 18;13(1):6277. doi: 10.1038/s41598-023-33508-1.


DOI:10.1038/s41598-023-33508-1
PMID:37072485
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10113239/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/ce87c9c32b93/41598_2023_33508_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/3ee0191e2e2a/41598_2023_33508_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/7c4c2faac9f5/41598_2023_33508_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/78afdd012f59/41598_2023_33508_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/eec473cda26b/41598_2023_33508_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/5e8c8c7e7707/41598_2023_33508_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/00ebce0fc22d/41598_2023_33508_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/ce87c9c32b93/41598_2023_33508_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/3ee0191e2e2a/41598_2023_33508_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/7c4c2faac9f5/41598_2023_33508_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/78afdd012f59/41598_2023_33508_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/eec473cda26b/41598_2023_33508_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/5e8c8c7e7707/41598_2023_33508_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/00ebce0fc22d/41598_2023_33508_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d7b/10113239/ce87c9c32b93/41598_2023_33508_Fig7_HTML.jpg

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本文引用的文献

[1]
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Front Oral Health. 2022-7-22

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