TGF-β-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine

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 (T RM ) are often defined as a non-circulating T cell population residing in non-lymphoid tissues. TILs carrying T RM features are associated with better tumor control. Here, we found that stem-like CD8 + T cells differentiated into T RM s in a TGF-β and tumor antigen dependent manner almost exclusively in tumor draining lymph node (TDLN). TDLN-resident stemlike T cells were negatively associated with the response to tumor vaccine. In other words, after tumor vaccine, TDLN stem-like T cells transiently lost T RM features, differentiated into migratory effectors and exerted tumor control.