The peripheral myeloid expansion driven by murine cancer progression is reversed by radiation therapy of the tumor

PLoS One. 2013 Jul 25;8(7):e69527. doi: 10.1371/journal.pone.0069527. Print 2013.

Abstract

Expansion of myeloid-lineage leukocytes in tumor-bearing mice has been proposed as a cause of systemic immunosuppression. We demonstrate that radiation therapy of tumors leads to a decline in myeloid cell numbers in the blood and a decrease in spleen size. The frequency of myeloid cells does not decline to the level seen in tumor-free mice: we demonstrate that metastatic disease can prevent myeloid cell numbers from returning to baseline, and that tumor recurrence from residual disease correlates with re-expansion of myeloid lineage cells. Radiation therapy results in increased proliferation of T cells in the spleen and while T cell responses to foreign antigens are not altered by tumor burden or myeloid cell expansion, responses to tumor-associated antigens are increased after radiation therapy. These data demonstrate that myeloid cell numbers are directly linked to primary tumor burden, that this population contracts following radiation therapy, and that radiation therapy may open a therapeutic window for immunotherapy of residual disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Animals
  • Antigens, Neoplasm / immunology
  • Cell Count
  • Cell Proliferation
  • Female
  • Gamma Rays / therapeutic use*
  • Immune Tolerance
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / radiotherapy*
  • Mice
  • Myeloid Cells / immunology
  • Myeloid Cells / pathology
  • Myeloid Cells / radiation effects*
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / radiotherapy*
  • Skin
  • Spleen / immunology
  • Spleen / pathology
  • Spleen / radiation effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • T-Lymphocytes / radiation effects*
  • Transplantation, Heterotopic
  • Tumor Burden / radiation effects*

Substances

  • Antigens, Neoplasm

Grant support

This study was supported by research funding from a Susan G Komen For the Cure Career Catalyst Award (KG110131) and an American Cancer Society Research Scholar Grant (RSG-12-168-01-LIB) to MJG, and a Wayne D. Kuni and Joan E. Kuni Foundation Kuni Scholar Award to MRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.