Inosine shapes PD-1 blockade responses and synergizes with dual PD-1/CTLA-4 immunotherapy to enhance antitumor immunity.

ABSTRACT: Inosine, a bacterial metabolite and agonist of the adenosine A2A receptor, modulates antitumor immunity. However, its precise effects on immune checkpoint inhibitors remain unclear. This study aimed to evaluate the impact of inosine on the efficacy of anti-programmed cell death protein 1 (PD-1) therapy and explore strategies to counteract any potential inhibitory effects. In in vitro co-culture systems, inosine selectively suppressed cancer cell growth without impairing T-cell viability. In a murine subcutaneous tumor model, inosine treatment reduced tumor growth and was associated with elevated interferon-gamma levels in the tumor microenvironment, along with increased infiltration by tumor-infiltrating lymphocytes and enhanced splenic CD4⁺ and CD8⁺ T-cell frequencies. However, the combin

SUBMITTER: Narikawa Y 

PROVIDER: S-EPMC12364772 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature