First Author | Mattarollo SR | Year | 2011 |
Journal | Cancer Res | Volume | 71 |
Issue | 14 | Pages | 4809-20 |
PubMed ID | 21646474 | Mgi Jnum | J:174069 |
Mgi Id | MGI:5051855 | Doi | 10.1158/0008-5472.CAN-11-0753 |
Citation | Mattarollo SR, et al. (2011) Pivotal Role of Innate and Adaptive Immunity in Anthracycline Chemotherapy of Established Tumors. Cancer Res 71(14):4809-4820 |
abstractText | 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-gamma production. Doxorubicin treatment enhances tumor antigen-specific proliferation of CD8 T cells in tumor-draining lymph nodes and promotes tumor infiltration of activated, IFN-gamma-producing CD8 T cells. Optimal doxorubicin treatment outcome also requires both interleukin (IL)-1beta and IL-17 cytokines, as blockade of IL-1beta/IL-1R or IL-17A/IL-17Ralpha signaling abrogated the therapeutic effect. IL-23p19 had no observed role. The presence of gammadelta T cells, but not Jalpha18(+) natural killer T cells, at the time of doxorubicin treatment was also important. In tumor samples taken from breast cancer patients prior to treatment with anthracycline chemotherapy, a correlation between CD8alpha, CD8beta, and IFN-gamma gene expression levels and clinical response was observed, supporting their role in the therapeutic efficacy of anthracyclines in humans. Overall, these data strongly support the pivotal contribution of both innate and adaptive immunity in treatment outcomes of anthracycline chemotherapy. Cancer Res; 71(14); 4809-20. (c)2011 AACR. |