Macrophage IL-10 Blocks CD8+ T Cell-dependent Responses to Chemotherapy by Suppressing IL-12 Expression in Intratumoral Dendritic Cells

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2014 Dec 3

PMID 25446896

Citations 535

Authors

Brian Ruffell

Debbie Chang-Strachan

Vivien Chan

Alexander Rosenbusch

Christine M T Ho

Nancy Pryer

Dylan Daniel

E Shelley Hwang

Hope S Rugo

Lisa M Coussens

Affiliations

Soon will be listed here.

Abstract

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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