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

Brian Ruffell, Debbie Chang-Strachan, Vivien Chan, Alexander Rosenbusch, Christine M T Ho, Nancy Pryer, Dylan Daniel, E. Shelley Hwang, Hope S. Rugo, Lisa Coussens

Research output: Contribution to journalArticle

253 Citations (Scopus)

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+ Tcell-dependent, but IL-10 did not directly suppress CD8+ Tcells 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.

Original languageEnglish (US)
Pages (from-to)623-637
Number of pages15
JournalCancer Cell
Volume26
Issue number5
DOIs
StatePublished - Nov 10 2014

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Interleukin-12
Interleukin-10
Dendritic Cells
Macrophages
T-Lymphocytes
Drug Therapy
Macrophage Colony-Stimulating Factor
Paclitaxel
Interleukin-10 Receptors
Breast Neoplasms
Interleukins
Carboplatin
Neoplasms
Phenotype
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Macrophage IL-10 Blocks CD8+ T Cell-Dependent Responses to Chemotherapy by Suppressing IL-12 Expression in Intratumoral Dendritic Cells. / Ruffell, Brian; Chang-Strachan, Debbie; Chan, Vivien; Rosenbusch, Alexander; Ho, Christine M T; Pryer, Nancy; Daniel, Dylan; Hwang, E. Shelley; Rugo, Hope S.; Coussens, Lisa.

In: Cancer Cell, Vol. 26, No. 5, 10.11.2014, p. 623-637.

Research output: Contribution to journalArticle

Ruffell, B, Chang-Strachan, D, Chan, V, Rosenbusch, A, Ho, CMT, Pryer, N, Daniel, D, Hwang, ES, Rugo, HS & Coussens, L 2014, 'Macrophage IL-10 Blocks CD8+ T Cell-Dependent Responses to Chemotherapy by Suppressing IL-12 Expression in Intratumoral Dendritic Cells', Cancer Cell, vol. 26, no. 5, pp. 623-637. https://doi.org/10.1016/j.ccell.2014.09.006
Ruffell, Brian ; Chang-Strachan, Debbie ; Chan, Vivien ; Rosenbusch, Alexander ; Ho, Christine M T ; Pryer, Nancy ; Daniel, Dylan ; Hwang, E. Shelley ; Rugo, Hope S. ; Coussens, Lisa. / Macrophage IL-10 Blocks CD8+ T Cell-Dependent Responses to Chemotherapy by Suppressing IL-12 Expression in Intratumoral Dendritic Cells. In: Cancer Cell. 2014 ; Vol. 26, No. 5. pp. 623-637.
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