Intratumoral radiation dose heterogeneity augments antitumor immunity in mice and primes responses to checkpoint blockade.

ABSTRACT: Radiation therapy (RT) activates multiple immunologic effects in the tumor microenvironment (TME), with diverse dose-response relationships observed. We hypothesized that, in contrast with homogeneous RT, a heterogeneous RT dose would simultaneously optimize activation of multiple immunogenic effects in a single TME, resulting in a more effective antitumor immune response. Using high-dose-rate brachytherapy, we treated mice bearing syngeneic tumors with a single fraction of heterogeneous RT at a dose ranging from 2 to 30 gray. When combined with dual immune checkpoint inhibition in murine models, heterogeneous RT generated more potent antitumor responses in distant, nonirradiated tumors compared with any homogeneous dose. The antitumor effect after heterogeneous RT required CD4 and CD8 T c

SUBMITTER: Jagodinsky JC 

PROVIDER: S-EPMC11522033 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature