PD-1+CD28H+ selectively identifies for superior tumor-reactive T lymphocytes in pancreatic cancer (TUM7P.1013)

Abstract

Abstract Tumor-infiltrating lymphocytes (TILs) are enriched in tumor-specific T cells and have been used as a source for adaptive cell therapy (ACT) of cancer. TILs are a mixture of different T cell subsets with both anti-tumor and pro-tumor capacities. It is valuable to isolate potent tumor-reactive T cells while eliminating suppressor T cells from TILs to maximize anti-tumor immune response. CD28H is a newly discovered co-receptor of the B7 family that interacts with its ligand B7-H5 to costimulate human T cells. CD28H is constitutively expressed on native T cells. However, repetitive antigenic exposure induces the loss of CD28H expression in T cells. T cells that have lost CD28H have the phenotypic characteristics of terminally differentiated and replicative senescent cells. Here we characterized PBMCs and TILs from patients with pancreatic cancer based on the expression of CD28H and PD-1. We found that a subset of T cells, PD-1+CD28H+ (DP) cells, are exclusively enriched in TILs. Based on phenotypic and functional analysis, our preliminary results suggest that PD-1+CD28H+ cells represent a subset of superior tumor-reactive cells in TILs. By targeting these DP cells by CD28H agonistic mAb and/or with a PD-1 blocking antibody, we are expecting to reprogram TIL functions in human pancreatic cancer.