Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells
By B. Ruffell, Debbie Chang-Strachan, Vivien W. Chan, Alexander Rosenbusch, C. Ho, N. Pryer, D. Daniel, E. Hwang, H. Rugo, Lisa M. Coussens. Cancer Cell, 2014
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Summary Blockade of colony-stimulating factor-1 (CSF-1) limits macrophage infiltration and improves response of mammary carcinomas to chemotherapy. Herein we identify interleukin (IL)-10 expression by macrophages as the critical mediator of this phenotype. Infiltrating macrophages were the primary source of IL-10 within tumors, and therapeutic blockade of IL-10 receptor (IL-10R) was equivalent to CSF-1 neutralization in enhancing primary tumor response to paclitaxel and carboplatin. Improved response to chemotherapy was CD8+ T cell-dependent, however IL-10 did not directly suppress CD8+ T cells or alter macrophage polarization. Instead, IL-10R blockade increased intratumoral dendritic cell expression of IL-12, which was necessary for improved outcomes. In human breast cancer, expression of IL12A and cytotoxic effector molecules were predictive of pathological complete response rates to paclitaxel.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/647280776f5d32e20fe3f65681a8ab80d3361ae0
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Citations in the corpus
- Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy (2016, neutral): “CD103+ DC-like cells are important in regu- lating antitumor immunity because they have enhanced abilities to activate CD8+ T cells compared to CD103– DCs and tumor- associated macrophages (Broz et al., 2014; Ruffell et al., 2014; Spranger et al., 2015).”
- Dendritic Cells and Cancer Immunity (2016, background): “This is not to imply that cDCs are operating at peak capacity, especially considering limitations on their infiltration and maturation status [7, 21], as well as suppressive pathways that may block particular functions [28, 29].”
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- Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. (2015, background): “…relies on the critical contribution of a particular subset of dendritic cells (DCs) that are endowed with potent phagocytic activity, and (in mice) express CD8a as well as tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, best known as CD134) (Broz et al., 2014; Ruffell et al., 2014).”
- Roles of the immune system in cancer: from tumor initiation to metastatic progression (2018, background): “…molecules such as IL-10, TGF-β , and prostaglandins; they also inhibit the secretion of IL-12 by DCs, avoiding the mounting of a Th-1 response and excluding NK and effector T cells (Ruffell et al. 2014; Speiser et al. 2016; Fry-drychowicz et al. 2017; Mantovani et al. 2017; Tauriello et al. 2018).”
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