Anti-metabolite chemotherapy increases LAG-3 expressing tumor-infiltrating lymphocytes which can be targeted by combination immune checkpoint blockade.

ABSTRACT:

Background

Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein/ligand 1 (PD-1/PD-L1) are approved for treatment of multiple cancer types. Chemotherapy is often administered with immune checkpoint blockade (ICB) therapies that target CTLA-4 and/or PD-(L)1. ICB targeting other immune checkpoints such as lymphocyte activating gene-3 (LAG-3) has the potential to improve antitumor responses when combined with chemotherapy. Response to anti-PD-1 ICB is dependent on progenitor exhausted CD8⁺ T cells (T_PEX) in the tumor, but it is unclear how chemotherapy alters T_PEX proportions and phenotype.

Methods

Here we investigated whether sequential chemotherapy altered T_PEX fre

SUBMITTER: Principe N 

PROVIDER: S-EPMC11440230 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature