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

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

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE193594 | GEO | 2023/11/01

REPOSITORIES: GEO

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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 [3' single-cell RNA-seq]

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

| PRJNA796815 | ENA

Diverse effect of WWOX overexpression in HT29 and SW480 colon cancer cell lines.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-01-23 | E-GEOD-54301 | biostudies-arrayexpress

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

2016-11-02 | GSE74604 | GEO

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