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Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE200133 | GEO | 2023/07/12

REPOSITORIES: GEO

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Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells [mCRC]

Project description:Colorectal tumors are often densely infiltrated by immune cells that have a role in surveillance and modulation of tumor progression but are burdened by exhaustion mechanisms fueled by the tumor microenvironment, which must be counteracted to achieve control. Here, we deployed a multidimensional approach to unravel the T cell functional landscape in tumor and peritumoral tissues from primary colorectal cancers and liver metastases. We found that T-cells are mainly localized at the front edge and that tumor-infiltrating T cells co-express multiple inhibitory receptors and highlighted CD39 as the major driver of exhaustion in both primary and metastatic colorectal tumors. By CRISPR/Cas9 genome editing tools, we simultaneously redirected T-cell specificity employing a novel T-cell receptor targeting the HER-2 antigen, and disrupted CD39, thus generating triple-knockout engineered lymphocytes. We showed that the absence of CD39 confers HER2-specific T cells a functional advantage in eliminating HER2+ patient-derived organoids, starring the relevance of the CD39 axis for further exploitation in adoptive T-cell therapy strategies to treat primary and metastatic colorectal cancer.

2023-07-12 | GSE200129 | GEO

Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells [NanoString]

2023-07-12 | GSE200131 | GEO

Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells [CRC]

2023-07-12 | GSE200130 | GEO

Systemic treatment of liver metastases from colorectal cancer.

Project description: Not available

| S-EPMC3630480 | biostudies-literature

Treatment of colorectal liver metastases.

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Differential analysis revealing APOC1 to be a diagnostic and prognostic marker for liver metastases of colorectal cancer.