Tumor regulation of myeloid-derived suppressor cell proliferation and trafficking

Ibrahim H. Younos, Alicia J. Dafferner, Dumrul Gulen, Holly C. Britton, James E. Talmadge

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

A stress response can induce myeloid progenitor cell (MPC) proliferation, mobilization, and extramedullary hematopoiesis (EMH) within lymphoid and parenchymal organs. Our studies using in vivo BrdU labeling, Ki-67 IHC staining, and carboxyfluorescein succinimidyl ester (CFSE) adoptive cell transfer revealed that spleens, rather than bone marrow (BM) and peripheral blood (PB), from 4T1 mammary tumor-bearing (TB) mice were the primary site of MPC proliferation. The resultant increase in MPCs was associated with tumor hematopoietic growth factor (GF) transcription, decreased apoptosis, as well as, prolonged survival of splenic MPCs. In naïve mice, i.v. injected CFSE-labeled MDSCs (myeloid-derived suppressor cells) initially accumulated in the lungs, while in TB mice, they rapidly sequestered in the spleen. In contrast, a few of the injected MDSCs and leukocytes arrested, proliferated, or accumulated in the marrow, tumor, or PB of TB mice. However, BrdU labeling revealed a significant demargination of proliferating splenic MPCs into the PB. In tumors, despite high GF transcript levels, we found that a high frequency of MDSCs was apoptotic. In summary, tumor growth and cytokines regulate MPC proliferation, trafficking, accumulation, apoptosis, and survival.

Original languageEnglish
Pages (from-to)245-256
Number of pages12
JournalInternational Immunopharmacology
Volume13
Issue number3
DOIs
Publication statusPublished - Jul 2012

Keywords

  • G-CSF
  • MDSC
  • NOS-2
  • Proliferation
  • Trafficking

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

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