Oral squamous cell carcinomas drive monocytes into immunosuppressive CD25+CD163+CD206+ macrophages
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1111562 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tumor-associated macrophages (TAMs) are major cellular components in the tumor microenvironment of oral squamous cell carcinomas (OSCCs). Most of these TAMs derive from circulating monocytes that differentiate in situ. In this work, we show that cell culture media (CM) derived from two OSCC cell lines, H413 and TR146, promote monocyte differentiation into M2 macrophages, characterized by a high expression of CD163, CD206 and a low expression of CD11c, CD86 and HLA-DR. These monocyte-derived macrophages (moMΦ) differentiated by CM from H413 cells were unable to activate allogeneic T cells, and inhibited T cell activation and proliferation induced by CD3/CD28 stimulation. By culturing monocytes with fractionated H413-CM, we found that soluble proteins mediated CD163+CD206+ moMΦ differentiation, discarding a role for small metabolites and extracellular vesicles. Differential proteomic analyses on H413-CM fractions revealed the presence of several proteins, including the complement factor H or plasminogen activator inhibitor, as potential candidates to induce CD163+CD206+ moMΦ differentiation. Finally, RNAseq transcriptomic analyses of H413 CM conditioned moMΦ, identified a signature expression profile involving cytokines and cytokine receptors, which surprisingly included IL2RA (CD25). CD25 enhanced expression was confirmed on H143-CM moMΦ. Collectively, these data indicate that the CM from OSCC cell lines promotes the differentiation of monocytes into functionally immunosuppressive macrophages and overall, our work contributes to the understanding of how OSCCs create an immunosuppressive cellular environment that favors tumor growth.
2024-07-03 | GSE267476 | GEO
Project description:CD206 is a common marker of a putative immunosuppressive ‘M2’ state in tumor-associated macrophages (TAMs). We made a novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs. Early depletion of CD206+ macrophages and monocytes (Mono/Macs) led to the indirect loss of conventional type I dendritic cells (cDC1), CD8 T cells and NK cells in tumors. CD206+ TAMs robustly expressed CXCL9, contrasting with stress-responsive Spp1-expressing TAMs and immature monocytes, which became prominent with early depletion. CD206+ TAMs differentially attracted activated CD8 T cells, and the NK and CD8 T cells in CD206-depleted tumors were deficient in Cxcr3, and cDC1-supportive Xcl1 and Flt3l expression. Disrupting this key anti-tumor axis decreased tumor control by antigen-specific T cells in mice. In human cancers, a CD206Replete, but not a CD206Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, cDC1 and NK signatures, and associated with better survival. These findings negate the unqualified classification of CD206+ ‘M2-like’ macrophages as immunosuppressive.
2024-11-08 | GSE281345 | GEO
Project description:The direct and indirect effects of targeting specific tumor-associated macrophage (TAM) subsets in cancer are not well-defined. TAM targeting strategies are frequently based on the ‘M1’ or ‘M2’ polarization categories, even as substantial data challenges this binary modeling of macrophage cell state. One molecule consistently referenced as a delineator of a putative immunosuppressive ‘M2’ state is the surface protein CD206. We thus made a novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs and assess their correspondence with pro-tumoral immunity. Early, but not late depletion of CD206+ macrophages and monocytes (here, ‘Mono/Macs’) led to an indirect loss of a key anti-tumor network of NK cells, conventional type I dendritic cells (cDC1) and CD8 T cells. Among myeloid cells, we found that the CD206+ TAMs are the primary producers of CXCL9, and able to differentially attract activated CD8 T cells. In contrast, a population of stress-responsive TAMs (“Hypoxic” or Spp1+) and immature monocytes, which lack CD206 expression and become prominent following early depletion, expressed markedly diminished levels of CXCL9. Those NK and CD8 T cells which enter CD206-depleted tumors express vastly reduced levels of the corresponding receptor Cxcr3, the cDC1-attracting chemokine Xcl1 and cDC1 growth factor Flt3l transcripts. Consistent with the loss of this critical network, early CD206+ TAM depletion decreased tumor control by antigen specific CD8 T cells in mice. Likewise, in humans, the CD206Replete, but not the CD206Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, NK cell and stimulatory cDC1 gene signatures and transcriptomic signatures skewed towards CD206Replete Mono/Macs associated with better survival. Together, these findings negate the unqualified classification of CD206+ ‘M2-like’ macrophages as immunosuppressive and provide further evidence of the context-dependence of macrophage function in tumors.
2024-11-08 | GSE281471 | GEO
Project description:6 small intestinal macrophage subsets (CD4–Tim4–CD163–, CD4+Tim4–CD163–, CD4+Tim4+CD163–, CD4–Tim4–CD163+, CD4+Tim4–CD163+, CD4+Tim4+CD163+ ) from adult male C57BL/6J mice
| PRJNA973088 | ENA
Project description:To investigate the transcriptional profiles of distinct macrophage subsets residing within the inflammed RA synovium. RNA sequencing was perfomed on FACS sorted CD206+CD163+ and CD206-CD163- synovial tissue macrophages from RA synovial tissue and fluid samples.
2024-09-10 | GSE246421 | GEO
Project description:To better determine functional heterogenity of small intestinal macrophages, 6 subsets of were sorted for RNA sequencing based on expression of CD4, Tim4, and CD163
2023-08-18 | GSE232645 | GEO
Project description:Clostridioides difficile CD206 Genome sequencing and assembly
| PRJNA85781 | ENA
Project description:BACKGROUND & AIMS: Intestinal mononuclear phagocytes (MNP) are phenotypically similar, but have different functions. Macrophages contribute to the pathogenesis of inflammatory bowel disease (IBD). To understand this contribution it is necessary to distinguish macrophages from other MNPs, and identify functionally-different macrophage populations. We aimed to accurately identify intestinal macrophage populations, and to ascertain their functions in patients with inflammatory bowel disease (IBD). METHODS: We developed 12-parameter flow cytometry protocols to identify and characterise human intestinal MNPs. We then used RNA sequencing, qPCR, and flow cytometry to analyse colonic biopsies from patients with CD, UC, or non-inflamed controls, in a cross-sectional study. RESULTS: We unambiguously differentiate macrophage populations (CD45+CD64+ HLA-DR+) from dendritic cells (CD45+CD64- HLA-DR+ CD11c;). We identify two distinct subsets within the macrophage population, differentiated by their expression of the mannose receptor, CD206. Further examination of these macrophage sub-populations showed that CD206+ macrophages expressed markers consistent with a mature macrophage phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of Trem1. On the contrary, CD64+ HLA-DR- CD206- cells appear to be semi-mature intermediaries in the development of mature intestinal macrophages from their monocyte precursors. CONCLUSIONS: We identified and purified MNP and macrophage populations from human intestinal lamina propria. Thorough characterisation reveals that human colonic macrophages appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature they lose their proliferative properties and acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD.
2018-12-26 | GSE124350 | GEO
Project description:To investigate CD163-related signals and cytokine production, mRNA expression of resident peritoneal marophages derived from wild type mice and CD163-deficient mice was analyzed.
2021-03-01 | GSE111679 | GEO
Project description:Comparison of gene expression profile of CD4+ CD25+, CD4+ CD25- CD45RBlow LAG3+ and CD4+ CD25- CD45RBlow LAG3- T cells. Naive CD4+CD25-CD45RBhigh T cells were used as a reference for pair comparison with values from the three other subsets.
2009-08-19 | E-MEXP-1343 | biostudies-arrayexpress