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Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T cell Immunity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE174243 | GEO | 2021/05/12

REPOSITORIES: GEO

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Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity.

Project description:Immune checkpoint blockade (ICB) has been a remarkable clinical advance for cancer; however, the majority of patients do not respond to ICB therapy. We show that metastatic disease in the pleural and peritoneal cavities is associated with poor clinical outcomes after ICB therapy. Cavity-resident macrophages express high levels of Tim-4, a receptor for phosphatidylserine (PS), and this is associated with reduced numbers of CD8+ T cells with tumor-reactive features in pleural effusions and peritoneal ascites from patients with cancer. We mechanistically demonstrate that viable and cytotoxic anti-tumor CD8+ T cells upregulate PS and this renders them susceptible to sequestration away from tumor targets and proliferation suppression by Tim-4+ macrophages. Tim-4 blockade abrogates this sequestration and proliferation suppression and enhances anti-tumor efficacy in models of anti-PD-1 therapy and adoptive T cell therapy in mice. Thus, Tim-4+ cavity-resident macrophages limit the efficacy of immunotherapies in these microenvironments.

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Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T cell Immunity [scRNA-Seq]

Project description:Here we report transcriptional and TCR specificities associated with PSlow and PShigh CD8 T cells.

2021-05-12 | GSE174241 | GEO

Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T cell Immunity [RNA-Seq]

Project description:Here we report RNA sequencing data from sorted Tim-4low vs Tim-4high macrophages in steady-state (no tumor) mice and also MC38-LG-tumor-bearing animals that were treated with isotype or anti-Tim-4 antibody.

2021-05-12 | GSE174151 | GEO

Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T cell Immunity

Project description:Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T cell Immunity

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Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T cell Immunity [RNA-Seq]

Project description:Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T cell Immunity [RNA-Seq]

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Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T cell Immunity [scRNA-Seq]

Project description:Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T cell Immunity [scRNA-Seq]

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Dendritic cells maintain anti-tumor immunity by positioning CD8 skin-resident memory T cells.

Project description:Tissue-resident memory (TRM) T cells are emerging as critical components of the immune response to cancer; yet, requirements for their ongoing function and maintenance remain unclear. APCs promote TRM cell differentiation and re-activation but have not been implicated in sustaining TRM cell responses. Here, we identified a novel role for dendritic cells in supporting TRM to melanoma. We showed that CD8 TRM cells remain in close proximity to dendritic cells in the skin. Depletion of CD11c+ cells results in rapid disaggregation and eventual loss of melanoma-specific TRM cells. In addition, we determined that TRM migration and/or persistence requires chemotaxis and adhesion mediated by the CXCR6/CXCL16 axis. The interaction between CXCR6-expressing TRM cells and CXCL16-expressing APCs was found to be critical for sustaining TRM cell-mediated tumor protection. These findings substantially expand our knowledge of APC functions in TRM T-cell homeostasis and longevity.

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Lipids impair NK cell anti-tumor immunity and transcription

Project description:This SuperSeries is composed of the SubSeries listed below.

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FLI1 promotes IFN-γ-induced kynurenine production to impair anti-tumor immunity

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-04-18 | GSE247898 | GEO

Tissue-resident memory CD8+ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells.

Project description:Tissue-resident memory CD8+ T (Trm) cells mediate potent local innate and adaptive immune responses and play a central role against solid tumors. However, whether Trm cells cross-talk with dendritic cells (DCs) to support anti-tumor immunity remains unclear. Here we show that antigen-specific activation of skin Trm cells leads to maturation and migration to draining lymph nodes of cross-presenting dermal DCs. Tumor rejection mediated by Trm cells triggers the spread of cytotoxic CD8+ T cell responses against tumor-derived neo- and self-antigens via dermal DCs. These responses suppress the growth of intradermal tumors and disseminated melanoma lacking the Trm cell-targeted epitope. Moreover, analysis of RNA sequencing data from human melanoma tumors reveals that enrichment of a Trm cell gene signature associates with DC activation and improved survival. This work unveils the ability of Trm cells to amplify the breath of cytotoxic CD8+ T cell responses through DCs, thereby strengthening anti-tumor immunity.

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