MDR1 promotes CD8 T cell persistence in tumors and protects against cytotoxic chemotherapy.

ABSTRACT: Multidrug transporters, including multidrug resistance-1 (MDR1), are recognized chiefly for effluxing chemotherapeutic drugs out of tumor cells. However, they are also expressed in many normal cells and tissues, including lymphocytes, but their physiological role is less well-understood. Here, we investigated the role of MDR1 in tumor-specific CD8 T cells (TST), which are critical in antitumor immunity and key targets of immunotherapies. Using a clinically-relevant genetic liver cancer mouse model, we investigated the efflux dynamics of TST as they underwent activation, proliferation, and differentiation to dysfunctional states in tumor-bearing hosts. Surprisingly, we found that late-stage/terminally dysfunctional TST had the highest efflux capacity in both murine and human liver tumors. T

SUBMITTER: Brown LA 

PROVIDER: S-EPMC12622045 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature