Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM.

ABSTRACT: The immunosuppressive effects of chemotherapy present a challenge for designing effective cancer immunotherapy strategies. We hypothesized that although systemic chemotherapy (SC) exhibits negative immunologic effects, local chemotherapy (LC) can potentiate an antitumor immune response. We show that LC combined with anti-programmed cell death protein 1 (PD-1) facilitates an antitumor immune response and improves survival (P < 0.001) in glioblastoma. LC-treated mice had increased infiltration of tumor-associated dendritic cells and clonal expansion of antigen-specific T effector cells. In comparison, SC resulted in systemic and intratumoral lymphodepletion, with decreased immune memory in long-term survivors. Furthermore, adoptive transfer of CD8⁺ cells from LC-treated mice parti

SUBMITTER: Mathios D 

PROVIDER: S-EPMC5724383 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature