Tissue-Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD-1 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade

Pancreatic ductal adenocarcinoma (PDAC) has a poor clinical CD103^þCD39^þ T cells was also observed within the CD8^þ outlook. Responses to immune checkpoint blockade are suboptimal tumor-infiltrating lymphocytes population. The expression of and a much more detailed understanding of the tumor immune PD-1 ligands was limited largely to hemopoietic cells whilst TIGIT microenvironment is needed if this situation is to be improved. ligands were expressed widely within the tumor microenvironment. Here, we characterized tumor-infiltrating T-cell populations in Programmed death-ligand 1 and CD155 were expressed within patients with PDAC using cytometry by time of flight (CyTOF) the T-cell area of ectopic lymphoid structures and colocalized with and single-cell RNA sequencing. T cells were the predominant PD-1^þTIGIT^þ CD8^þ T cells. Combinatorial anti–PD-1 and TIGIT immune cell subset observed within tumors. Over 30% of CD4^þ T blockade enhanced IFNg secretion and proliferation of T cells cells expressed a CCR6^þCD161^þ Th17 phenotype and 17% in the presence of PD-1 and TIGIT ligands. As such, we showed displayed an activated regulatory T-cell profile. Large populations that the PDAC microenvironment is characterized by the presence of CD8^þ tissue-resident memory (TRM) T cells were also present of substantial populations of TRM cells with an exhausted and expressed high levels of programmed cell death protein 1 PD-1^þTIGIT^þ phenotype where dual checkpoint receptor blockade (PD-1) and TIGIT. A population of putative tumor-reactive represents a promising avenue for future immunotherapy.