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TGF--dependent Lymphoid Tissue Residency of Stem-like T cells Limits the Response to Tumor Vaccine

By Guo Li, Liwen Wang, Chaoyu Ma, Wei Liao, Yong Liu, Shruti Mishra, Xin Zhang, Yuanzheng Qiu, Qianjin Lu, Nu Zhang

Posted 19 Jul 2021
bioRxiv DOI: 10.1101/2021.07.19.452945

Stem-like CD8+ T cells represent the key subset responding to multiple tumor immunotherapies, including tumor vaccination. However, the signals that control the differentiation of stem-like T cells are not entirely known. Most previous investigations on stem-like T cells are focused on tumor infiltrating T cells (TIL). The behavior of stem-like T cells in other tissues remains to be elucidated. Tissue-resident memory T cells (TRM) are often defined as a non-circulating T cell population residing in non-lymphoid tissues. TILs carrying TRM features are associated with better tumor control. Here, we found that stem-like CD8+ T cells differentiated into TRMs in a TGF-{beta} and tumor antigen dependent manner almost exclusively in tumor draining lymph node (TDLN). TDLN-resident stem-like T cells were negatively associated with the response to tumor vaccine. In other words, after tumor vaccine, TDLN stem-like T cells transiently lost TRM features, differentiated into migratory effectors and exerted tumor control.

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