[PDF][PDF] Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells

B Ruffell, D Chang-Strachan, V Chan, A Rosenbusch… - Cancer cell, 2014 - cell.com
B Ruffell, D Chang-Strachan, V Chan, A Rosenbusch, CMT Ho, N Pryer, D Daniel…
Cancer cell, 2014cell.com
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 …
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, but 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.
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