Requirement for innate immunity and CD90⁺ NK1.1⁻ lymphocytes to treat established melanoma with chemo-immunotherapy.

ABSTRACT: We sought to define cellular immune mechanisms of synergy between tumor-antigen-targeted monoclonal antibodies and chemotherapy. Established B16 melanoma in mice was treated with cytotoxic doses of cyclophosphamide in combination with an antibody targeting tyrosinase-related protein 1 (αTRP1), a native melanoma differentiation antigen. We find that Fcγ receptors are required for efficacy, showing that antitumor activity of combination therapy is immune mediated. Rag1(-/-) mice deficient in adaptive immunity are able to clear tumors, and thus innate immunity is sufficient for efficacy. Furthermore, previously treated wild-type mice are not significantly protected against tumor reinduction, as compared with mice inoculated with irradiated B16 alone, consistent with a primarily innate immune

SUBMITTER: Moskalenko M 

PROVIDER: S-EPMC4690202 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature