Pivotal Role of Innate and Adaptive Immunity in Anthracycline Chemotherapy of Established Tumors
Stephen R Mattarollo, Sherene Loi, Helene Duret, Yuting Ma, Laurence Zitvogel, Mark J Smyth
Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2011
We show, in a series of established experimental breast adenocarcinomas and fibrosarcomas induced by carcinogen de novo in mice, that the therapeutic efficacy of doxorubicin treatment is dependent on CD8 T cells and IFN-γ production. Doxorubicin treatment enhances tumor antigen-specific proliferation of CD8 T cells in tumor-draining lymph nodes and promotes tumor infiltration of activated, IFN-γ-producing CD8 T cells. Optimal doxorubicin treatment outcome also requires both interleukin (IL)-1β and IL-17 cytokines, as blockade of IL-1β/IL-1R or IL-17A/IL-17Rα signaling abrogated the therapeutic effect. IL-23p19 had no observed role. The presence of γδ T cells, but not Jα18(+) natural killer T..View full abstract
This work was supported by The Victorian Cancer Agency, The Victorian Breast Cancer Consortium, and the Susan G. Komen Breast Cancer Foundation. S.R. Mattarollo was supported by a Balzan Foundation Fellowship. S. Loi was supported by a National Health & Medical Research Council (NH&MRC) clinical fellowship. Y. Ma was supported by China Scholarship Council. L. Zitvogel was supported by LIGUE labellisee, INFLACARE FP7 EU grant, INCa, Fondation pour la Recherche Medicale, and Fondation de France. M.J. Smyth received support from an NH&MRC Australia Fellowship.