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

Cancer Cell. 2014 Nov 10;26(5):623-37. doi: 10.1016/j.ccell.2014.09.006. Epub 2014 Oct 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, CD
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / metabolism*
  • Female
  • Humans
  • Integrin alpha Chains
  • Interleukin-10 / physiology*
  • Interleukin-12 Subunit p35 / biosynthesis*
  • Interleukin-12 Subunit p35 / genetics
  • Macrophages
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / metabolism
  • Mice, Transgenic
  • Paclitaxel / pharmacology*
  • Receptors, Interleukin-10 / antagonists & inhibitors
  • Receptors, Interleukin-10 / metabolism


  • Antigens, CD
  • Antineoplastic Agents, Phytogenic
  • IL10 protein, mouse
  • IL12A protein, human
  • Integrin alpha Chains
  • Interleukin-12 Subunit p35
  • Receptors, Interleukin-10
  • alpha E integrins
  • Interleukin-10
  • Paclitaxel