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

Ruffell, B and Chang-Strachan, D and Chan, V and Rosenbusch, A and Ho, CM and Pryer, N and Daniel, D and Hwang, ES and Rugo, HS and Coussens, LM (2014) Macrophage IL-10 Blocks CD8(+) T Cell-Dependent Responses to Chemotherapy by Suppressing IL-12 Expression in Intratumoral Dendritic Cells. Cancer Cell. pp. 623-637.

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. Copyright 2014 Elsevier Inc. All rights reserved

Item Type: Article
Additional Information: NIBR author: Chang-Strachan, D institute: NIBR contributor address: Department of Cell, Developmental & Cancer Biology and Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Date Deposited: 13 Oct 2015 13:11
Last Modified: 13 Oct 2015 13:11
URI: https://oak.novartis.com/id/eprint/24936

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