Dataset Information

Human peritoneal CCR2LowCRIgHigh macrophage subset exhibits embryonic origin-like phenotypes

ABSTRACT: maintained by the differentiation of bone marrow-derived monocytes and the proliferation of macrophages originating from yolk sac or fetal liver. However, to what extent this paradigm shift is the case for human tissues is not fully understood. Here, we detect a human peritoneal macrophage subset which exhibits embryonic origin-like phenotypes. Macrophages in ascites of patients with gastric cancers were divided into CCR2Low and CCR2High subsets, the ratio of which was variable among donors. The gene expression profiles of these subsets were similar to those of macrophage subsets in hearts. CRIg was recently reported as a marker to distinguish two macrophage subsets in ascites of patients with cirrhosis. CCR2Low and CCR2High subsets identified in this study expressed CRIg at high and low levels, respectively. Importantly, the CCR2LowCRIgHigh subset expressed the cell proliferation marker Ki67 and recently-proposed core markers for macrophages with embryonic origin (TIMD4, LYVE1, and FOLR2) at higher levels than those of the CCR2HighCRIgLow subset. Moreover, many other markers shared by TIMD4+LYVE1+FOLR2+ macrophages in heart, lung, kidney and liver exhibited a similar expression pattern in the peritoneal CCR2LowCRIgHigh subset. These results suggest that the CCR2LowCRIgHigh subset in peritoneal cavity contains macrophages with embryonic origin.

ORGANISM(S): Homo sapiens

PROVIDER: GSE308456 | GEO | 2025/09/23

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) which can either promote tumor progression (M2) or induce antitumor immunity (M1). The hypothesis of our study is that the expression of FOLR2 is associated with an M2-like macrophage profile. The main goal of this study is to compare the transcriptomic profile of FOLR2 positive and FOLR2 negative TAMs obtained from the ascites of C57BL/6 mice bearing ovarian ID8 intraperitoneal tumors. Abstract: The immunosuppressive tumor microenvironment (TME) represents a major barrier for effective immunotherapy. Tumor-associated macrophages (TAMs) are highly heterogeneous and plastic cell components of the TME which can either promote tumor progression (M2-like) or boost antitumor immunity (M1-like). Selective targeting of the pro-tumorigenic subset of TAMs represents an attractive therapeutic strategy. Here, we demonstrate that a subset of TAMs that expressing folate receptor β (FRβ) possess an immunosuppressive, tumor-promoting M2-like profile, while FRβ negative TAMs feature pro-inflammatory M1 macrophage properties. In syngeneic tumor mouse models, the administration of FRβ-targeted chimeric antigen receptor (CAR) T-cells mediated elimination of FRβ+ TAMs in the TME, which resulted in an enrichment of pro-inflammatory monocytes, an influx of endogenous tumor-specific CD8+ T-cells, delayed tumor progression, and prolonged survival. Preconditioning of the TME with FRβ-specific CAR T-cells also improved the effectiveness of tumor-directed anti-mesothelin CAR T-cells, while simultaneous co-administration of both CAR products did not. Thus, CAR T-cell-mediated depletion of immunosuppressive M2-like TAMs incites a pro-inflammatory TME that broadens endogenous antitumor immunity and limits tumor progression, highlighting the pro-tumor role of FRβ+ TAMs in the TME and the therapeutic implications of TAM-depleting agents as preparative adjuncts to conventional immunotherapies that directly target tumor antigens.

Dataset Information

Human peritoneal CCR2LowCRIgHigh macrophage subset exhibits embryonic origin-like phenotypes

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets