Abstract
T cell exhaustion is a main obstacle against effective cancer immunotherapy. Exhausted T cells include a subpopulation that maintains proliferative capacity, referred to as precursor exhausted T cells (T(PEX)). While functionally distinct and important for antitumor immunity, T(PEX) possess some overlapping phenotypic features with the other T-cell subsets within the heterogeneous tumor-infiltrating T-lymphocytes (TIL). Here we explore surface marker profiles unique to T(PEX) using the tumor models treated by chimeric antigen receptor (CAR)-engineered T cells. We find that CD83 is predominantly expressed in the CCR7(+)PD1(+) intratumoral CAR-T cells compared with the CCR7(-)PD1(+) (terminally differentiated) and CAR-negative (bystander) T cells. The CD83(+)CCR7(+) CAR-T cells exhibit superior antigen-induced proliferation and IL-2 production compared with the CD83(-) T cells. Moreover, we confirm selective expression of CD83 in the CCR7(+)PD1(+) T-cell population in primary TIL samples. Our findings identify CD83 as a marker to discriminate T(PEX) from terminally exhausted and bystander TIL.