Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated.
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) are deficient in inflammatory functions and that this impairment is associated with diminished expression of transcription factors nuclear factor kappaB 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 kappaB down-regulation, 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-beta and prostaglandin E(2), two immunosuppressive tumor-derived factors, may be involved in this phenomenon.
Torroella-Kouri
Marta
M
Department of Microbiology and Immunology, University of Miami School of Medicine, Sylvester Cancer Center, Miami, Florida 33101, USA.
Silvera
Risset
R
Rodriguez
Dayron
D
Caso
Raul
R
Shatry
Alwi
A
Opiela
Shannon
S
Ilkovitch
Dan
D
Schwendener
Reto A
RA
Iragavarapu-Charyulu
Vijaya
V
Cardentey
Yoslayma
Y
Strbo
Natasa
N
Lopez
Diana M
DM
D016475:3T3 Cells; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D004002:Clodronic Acid / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D004002:Clodronic Acid; D015232:Dinoprostone