Obesity triggers enhanced MDSC accumulation in murine renal tumors via elevated local production of CCL2. Academic Article uri icon

Overview

abstract

  • Obesity is one of the leading risk factors for developing renal cell carcinoma, an immunogenic tumor that is treated clinically with immunostimulatory therapies. Currently, however, the mechanisms linking obesity with renal cancer incidence are unclear. Using a model of diet-induced obesity, we found that obese BALB/c mice with orthotopic renal tumors had increased total frequencies of myeloid-derived suppressor cells (MDSC) in renal tumors and spleens by d14 post-tumor challenge, relative to lean counterparts. Renal tumors from obese mice had elevated concentrations of the known myeloid cell chemoattractant CCL2, which was produced locally by increased percentages of dendritic cells, macrophages, B cells, and CD45- cells in tumors. MDSC expression of the CCL2 receptor, CCR2, was unaltered by obesity but greater percentages of CCR2+ MDSCs were present in renal tumors from obese mice. Of note, the intracellular arginase levels and per-cell suppressive capacities of tumor-infiltrating and splenic MDSCs were unchanged in obese mice relative to lean controls. Thus, our findings suggest that obesity promotes renal tumor progression via development of a robust immunosuppressive environment that is characterized by heightened local and systemic MDSC prevalence. Targeted intervention of the CCL2/CCR2 pathway may facilitate immune-mediated renal tumor clearance in the obese.

publication date

  • March 13, 2015

Research

keywords

  • Chemokine CCL2
  • Kidney Neoplasms
  • Myeloid Cells
  • Obesity

Identity

PubMed Central ID

  • PMC4358922

Scopus Document Identifier

  • 84929497622

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-09-3690

PubMed ID

  • 25769110

Additional Document Info

volume

  • 10

issue

  • 3