Dataset Information

Tumor Antigen–Independent Targeting of Solid Tumors by Armored 1 Macrophage-Directed anti-TREM2-CAR T Cells

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy has shown remarkable clinical efficacy in hematological malignancies and, more recently, in autoimmune diseases. However, its application in solid tumors has been limited by tumor antigen heterogeneity, antigen escape, and the immunosuppressive tumor microenvironment (TME), which is particularly shaped by tumor associated macrophages (TAMs). To overcome these barriers, we developed a novel CAR T cell strategy targeting human TREM2⁺ immunosuppressive TAMs. Macrophage-directed anti- TREM2-CAR T cells demonstrated potent anti-TREM2 activity in both in vitro assays and in solid tumor models in vivo. To further enhance intratumoral T cell function, we incorporated a CAR T cell responsive synthetic DNA biosensor comprising NFAT motifs that enable localized secretion of interleukin-12 upon CAR activation. In murine tumor models, this “armored” TREM2-targeted CAR-T cell approach led to robust remodeling of the TME and tumor-draining lymph nodes, characterized by TREM2⁺ TAM depletion, enhanced T and NK cell infiltration and activation, and complete tumor eradication, independent of tumor antigen expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE304568 | GEO | 2026/07/29

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

Tumor Antigen–Independent Targeting of Solid Tumors by Armored 1 Macrophage-Directed anti-TREM2-CAR T Cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets