Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated

Marta Torroella-Kouri, Risset Silvera, Dayron Rodriguez, Raul Caso, Alwi Shatry, Shannon Opiela, Dan Ilkovitch, Reto A. Schwendener, Vijaya Iragavarapu-Charyulu, Yoslayma Cardentey, Natasa Strbo, Diana M. Lopez

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Systemic and local immune deficiency is associated with cancer, and the role of M2 tumor-associated macrophages in this phenomenon is well recognized. However, the immune status of macrophages from peripheral compartments in tumor hosts is unclear. Peritoneal macrophages (PEM)are derived from circulating monocytes and recruited to the peritoneal cavity where they differentiate into macrophages. We have previously shown that PEMs from mice bearing D1-DMBA-3 mammary tumors (T-PEM)ar e deficient in inflammatory functions and that this impairment is associated with diminished expression of transcription factors nuclear factor κB and CAAT/enhancer-binding protein. We now provide evidence that T-PEMs display neither M1 nor M2 phenotypes, yet exhibit deficiencies in the expression of several inflammatory cytokines and various proinflammatory signaling pathways. Moreover, due to nuclear factor κB downregulation, increased apoptosis was observed in T-PEMs. We report for the first time that macrophage depletion is associated with increased macrophage progenitors in bone marrow. Furthermore, T-PEMs have a lower expression of macrophage differentiation markers F4/80, CD68, CD115, and CD11b, whereas Gr-1 is up-regulated. Our results suggest that T-PEMs are less differentiated and represent a newly derived population from blood monocytes. Lastly, we show that transforming growth factor-B and prostaglandin E2, two immunosuppressive tumor-derived factors, may be involved in this phenomenon.

Original languageEnglish (US)
Pages (from-to)4800-4809
Number of pages10
JournalCancer Research
Issue number11
StatePublished - Jun 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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