PI3Kδ/γ inhibitor BR101801 extrinsically potentiates effector CD8⁺ T cell-dependent antitumor immunity and abscopal effect after local irradiation.

ABSTRACT:

Background

Radiotherapy enhances antitumor immunity. However, it also induces immunosuppressive responses, which are major hurdles for an effective treatment. Thus, targeting the immunosuppressive tumor microenvironment is essential for enhancing the antitumor immunity after radiotherapy. Retrospective studies show that a blockade of PI3Kδ and/or γ, which are abundant in leukocytes, exhibits antitumor immune response by attenuating activity of immune suppressive cells, however, the single blockade of PI3Kδ or γ is not sufficient to completely eliminate solid tumor.

Methods

We used BR101801, PI3Kδ/γ inhibitor in the CT-26 syngeneic mouse model with a subcutaneously implanted tumor. BR101801 was administered daily, and the target tumor site was locally irradiated. We monitored

SUBMITTER: Yoon YN 

PROVIDER: S-EPMC8921929 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature