PD-1/CTLA-4 Blockade Leads to Expansion of CD8⁺PD-1^int TILs and Results in Tumor Remission in Experimental Liver Cancer.

ABSTRACT:

Background

Checkpoint inhibitors act on exhausted CD8⁺ T cells and restore their effector function in chronic infections and cancer. The underlying mechanisms of action appear to differ between different types of cancer and are not yet fully understood.

Methods

Here, we established a new orthotopic HCC model to study the effects of checkpoint blockade on exhausted CD8⁺ tumor-infiltrating lymphocytes (TILs). The tumors expressed endogenous levels of HA, which allowed the study of tumor-specific T cells.

Results

The induced tumors developed an immune-resistant TME in which few T cells were found. The few recovered CD8⁺ TILs were mostly terminally exhausted and expressed high levels of PD-1. PD-1/CTLA-4 blockade resulted in a strong incre

SUBMITTER: Bufe S 

PROVIDER: S-EPMC10267567 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature