CD49a and CD103 expression on tumor infiltrating lymphocytes in B16-OVA tumors depends on location and is correlated with a naive phenotype

Tissue resident memory (T RM ) cells are found in certain peripheral tissues long after resolution of infections that generate them. T RM formation is induced by TGFβ and has been associated with upregulation of CD49a and CD103. Interaction of CD49a and CD103 with their respective ligands is thought to allow long term persistence of T RM cells in peripheral tissues. In melanoma patients, increased expression of CD49a and CD103 has been observed on tumor infiltrating lymphocytes (TIL) compared to PBMCs. These phenotypic similarities suggest that a subset of TIL might function as T RM. However, the impact of continuous antigen presentation and/or differential TGFβ expression levels on this property of TIL is currently unknown. Here we demonstrate that, in B16-OVA melanoma tumors, CD49a and CD103 expression on CD8 TILs is upregulated compared to lymph node (LN) derived CD8 T cells from non-tumor bearing mice. Additionally, relative expression of CD49a and CD103 differs between subcutaneous and intraperitoneal tumors. The capacity of T cells to persist in tumors thus potentially changes based on tumor location, which may be dependent on TGFβ levels. In contrast to LN of non-tumor bearing mice, CD103 is expressed on 50–90% of LN CD8 T cells in tumor bearing mice. Furthermore, CD103 + CD8 TILs have a more naive phenotype, whereas CD103 neg CD8 TILs mainly express memory/effector T cell markers. The opposite is observed when T cells are activated in vitro. These data suggest that CD103 + CD8 T cells in tumors are largely due to a tumor induced systemic induction of CD103 on naive T cells, rather than intratumoral T RM differentiation . The importance of CD103 in retaining naive T cells for functional differentiation within the tumor remains to be established.