Low-dose radiotherapy combined with dual PD-L1 and VEGFA blockade elicits antitumor response in hepatocellular carcinoma mediated by activated intratumoral CD8⁺ exhausted-like T cells.

ABSTRACT: Atezolizumab (anti-PD-L1) combined with bevacizumab (anti-VEGFA) is the first-line immunotherapy for advanced hepatocellular carcinoma (HCC), but the number of patients who benefit from this regimen remains limited. Here, we combine dual PD-L1 and VEGFA blockade (DPVB) with low-dose radiotherapy (LDRT), which rapidly inflames tumors, rendering them vulnerable to immunotherapy. The combinatorial therapy exhibits superior antitumor efficacy mediated by CD8⁺ T cells in various preclinical HCC models. Treatment efficacy relies upon mobilizing exhausted-like CD8⁺ T cells (CD8⁺ Tex) with effector function and cytolytic capacity. Mechanistically, LDRT sensitizes tumors to DPVB by recruiting stem-like CD8⁺ Tpex, the progenitor exhausted CD8⁺ T

SUBMITTER: Li S 

PROVIDER: S-EPMC10673920 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature