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Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [3' single-cell RNA-seq]

ABSTRACT: Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [3' single-cell RNA-seq]

PROVIDER: PRJNA796815 | ENA |

REPOSITORIES: ENA

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Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [scRNA-seq]

Project description:Despite the high prognostic value of immune infiltrates in colorectal cancer (CRC), metastatic disease remains resistant to immunotherapy by immune checkpoint blockade (ICB). Here we show in a metastatic CRC multi-tumor preclinical model that orthotopically-implanted primary colon tumors can spontaneously exert a colon-specific and immune-dependent antimetastatic effect on distant hepatic lesions. An immune signature, integrating antitumor CD8 T cells, dendritic cells and protumor macrophages, that we called MicroEnvironment (ME)-score, was predictive of the antimetastatic effect. ScRNA-Seq and phenotypic analyses revealed that enterotropic α4β7 integrin expressing tumor neoantigen-specific CD8 T cells were key components of the systemic immune response responsible for the antimetastatic effect. Accordingly, the presence of concomitant colon tumors improved the efficacy of proof-of-concept ICB on liver lesions and generated a protective memory immune response whereas antibody-mediated partial depletion of α4β7+ cells abrogated the control of metastatic disease by the primary tumor. Finally, in a metastatic CRC patients’ cohort, we show increased expression of genes encoding the α4β7 integrin and of the ME-score in ICB responsive metastases concomitant with increased proportions of circulating α4β7+ CD8 T cells. Our findings identify a systemic cancer immunosurveillance role for gut primed tumor-specific α4β7+ CD8 T cells.

2023-11-01 | GSE219087 | GEO

Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [bulk RNA-seq]

2023-11-01 | GSE193534 | GEO

Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [3' single-cell RNA-seq]

2023-11-01 | GSE193593 | GEO

Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells

Project description:Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells

| PRJNA796808 | ENA

Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [scRNA-seq]

Project description:Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [scRNA-seq]

| PRJNA907008 | ENA

Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [bulk RNA-seq]

Project description:Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [bulk RNA-seq]

| PRJNA796554 | ENA

Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells

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

2023-11-01 | GSE193594 | GEO

Phenotypic plasticity underlies local invasion and distant metastasis in colon cancer (Bulk RNA-Seq)

Project description:Phenotypic plasticity and partial EMT underlie local invasion and distant metastasis in colon cancer. CD44highEpCAMhigh and CD44highEpCAMlow RNAseq profiles of colon cancer cell lines HCT116 and SW480.

2020-07-23 | GSE154927 | GEO

Phenotypic plasticity underlies local invasion and distant metastasis in colon cancer (Single cell RNA-Seq)

Project description:Phenotypic plasticity and partial EMT underlie local invasion and distant metastasis in colon cancer. CD44highEpCAMhigh and CD44highEpCAMlow single cell RNAseq profiles of colon cancer cell lines HCT116 and SW480.

2020-07-23 | GSE154930 | GEO

HIV-1 gp120 impairs B cell proliferation by inducing TGF-β1 production and FcRL4 expression via an α4β7-dependent mechanism

Project description:The anti-HIV humoral immune response following acute infection is delayed and ineffective. HIV envelope protein gp120 binds to and signals through α4β7 on T cells. We show that gp120 also binds and signals through α4β7 on B cells, resulting in an abortive proliferative response. In primary B cells, gp120 signaling through α4β7 resulted in increased expression of TGF-β1 and the B cell inhibitory receptor FcRL4. Co-culture of B cells with HIV-infected autologous CD4+ T cells also resulted in increased B cell FcRL4 expression. These findings indicate that, in addition to inducing chronic immune activation, viral proteins can contribute directly to HIV-associated B cell dysfunction, thus providing a mechanism whereby the virus subverts the early HIV-specific humoral immune response. Forty-two samples in two batches were run with different treatments and different time points.

2013-10-17 | E-GEOD-49019 | biostudies-arrayexpress

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