Medline ® Abstract for Reference 137
of 'Principles of cancer immunotherapy'
Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells.
Ruffell B, Chang-Strachan D, Chan V, Rosenbusch A, Ho CM, Pryer N, Daniel D, Hwang ES, Rugo HS, Coussens LM
Cancer Cell. 2014 Nov;26(5):623-37. 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.
Department of Cell, Developmental&Cancer Biology and Knight Cancer Institute, Oregon Health&Science University, Portland, OR 97239, USA.