Cxcr3 constrains pancreatic cancer dissemination through instructing T cell fate.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is a lethal and metastatic malignancy resistant to therapy. Elucidating how pancreatic tumor-specific T cells differentiate and are maintained in vivo could inform novel therapeutic avenues to promote T cell antitumor activity. Here, we show that the spleen is a critical site harboring tumor-specific CD8 T cells that functionally segregate based on differential Cxcr3 and Klrg1 expression. Cxcr3+ Klrg1- T cells express the memory stem cell marker Tcf1, whereas Cxcr3-Klrg1 + T cells express GzmB consistent with terminal differentiation. We identify a Cxcr3+ Klrg1+ intermediate T cell subpopulation in the spleen that is highly enriched for tumor specificity. However, tumor-specific T cells infiltrating primary tumors progressively downregulate both Cxcr3

SUBMITTER: Burrack AL 

PROVIDER: S-EPMC10198906 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature