title: Tumor microenvironment profoundly modifies functional status of macrophages: peritoneal and tumor-associated macrophages are two very different subpopulations.
abstract: Macrophages are key players in the inflammatory response. In this study, we tested the hypothesis that although all macrophage subpopulations in tumor hosts are affected by the disease, it is the close proximity to the tumor that induces major alterations in these cells. We compared tumor-associated macrophages (TAMs) with peritoneal macrophages from mice bearing D1-DMBA-3 mammary tumors (T-PEMs). Our results show that TAMs downregulate IL-12p70 but upregulate IL-12p40, IL-23, IL-6 and IL-10. Some NFκB and C/EBP transcription factors family members are decreased in TAMs; however NFκBp50 homodimers, STAT1/pSTAT1 and STAT3/pSTAT3 are overexpressed. Furthermore, while TAMs block T-cell proliferation and are more prone to apoptosis compared to T-PEMs, both types of macrophages have an impaired phagocytic capacity. Moreover, TAMs constitutively express iNOS and produce nitric oxide but do not express arginase and are Gr-1(high) and CD11b(low). Collectively, our analysis of two spatially distinct macrophage subpopulations in tumor-bearing mice revealed that the tumor modulates them differently into two molecularly and functionally dissimilar macrophage subpopulations.
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Dayron
authors.initials: D
authors.lastname: Rodríguez
authors.forename: Risset
authors.initials: R
authors.lastname: Silvera
authors.forename: Roberto
authors.initials: R
authors.lastname: Carrio
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Nadji
authors.forename: Raul
authors.initials: R
authors.lastname: Caso
authors.forename: Gracielena
authors.initials: G
authors.lastname: Rodríguez
authors.forename: Vijaya
authors.initials: V
authors.lastname: Iragavarapu-Charyulu
authors.forename: Marta
authors.initials: M
authors.lastname: Torroella-Kouri
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D059016:Tumor Microenvironment / Q000276:immunology*
keywords: Immunosuppression; Inflammation; MDSC; NPEM; Peritoneal and tumor-associated macrophages; TAM; TPEM; Treg; Tumor microenvironment; myeloid derived suppressor cell; normal peritoneal elicited macrophage; regulatory T cell; tumor associated macrophage; tumor peritoneal elicited macrophage