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Pivotal Role of Innate and Adaptive Immunity in Anthracycline Chemotherapy of Established Tumors
- Source :
- Cancer Research. 71:4809-4820
- Publication Year :
- 2011
- Publisher :
- American Association for Cancer Research (AACR), 2011.
-
Abstract
- 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 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 CD8α, CD8β, and IFN-γ 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. ©2011 AACR.
- Subjects :
- Male
Cancer Research
Anthracycline
CD8 Antigens
Fibrosarcoma
medicine.medical_treatment
Epitopes, T-Lymphocyte
Gene Expression
Mice, Transgenic
Adaptive Immunity
Adenocarcinoma
CD8-Positive T-Lymphocytes
Interferon-gamma
Mice
Lymphocytes, Tumor-Infiltrating
medicine
Animals
Cytotoxic T cell
Interferon gamma
Doxorubicin
Mice, Inbred BALB C
Chemotherapy
Antibiotics, Antineoplastic
business.industry
Interleukin-17
Mammary Neoplasms, Experimental
Interleukin
Natural killer T cell
Acquired immune system
Immunity, Innate
Mice, Inbred C57BL
Oncology
Immunology
Cancer research
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....ebfaa294d09934f6a6dea803b1ca06f3