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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ruffell, B; Chang-Strachan, D; Chan, V; Rosenbusch, A; Ho, CMT; Pryer, N; Daniel, D; Hwang, ES; Rugo, HS; Coussens, LM

Published Date

  • November 10, 2014

Published In

Volume / Issue

  • 26 / 5

Start / End Page

  • 623 - 637

PubMed ID

  • 25446896

Pubmed Central ID

  • 25446896

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2014.09.006

Language

  • eng

Conference Location

  • United States