Similar Datasets
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 | GSE200131 | GEO
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 | GSE200130 | GEO
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
Project description:Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells
| PRJNA823035 | ENA
Project description:Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells [mCRC]
| PRJNA823037 | ENA
Project description:Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells [CRC]
| PRJNA823036 | ENA
Project description:Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells [NanoString]
| PRJNA823039 | ENA
Project description:Patients presenting with synchronous or metachronous colorectal cancer liver metastases (CLM) should be evaluated for multimodal management with curative intent. Preoperative systemic chemotherapy shows beneficial impact on adjuvant progression-free survival and also borderline on overall survival, without significantly increasing initially R0 resectable patients postoperative complication rates. Postoperative chemotherapy recommended based on the perioperative trial experience for those patients achieving at least stable disease during preoperative chemotherapy, or based on the adjuvant trials for patients receiving upfront resection. 'Borderline' resectable CLM, preoperative chemotherapy plays an important role in both in achievement of a resectable status and improvement of prognosis. Recent 4 drug combinations demonstrated response rates up to 80% even for advanced disease and are thus promising regimens for further evaluation in patients with resectable or unresectable liver-limited (+/- lung) disease.
| S-EPMC3630480 | biostudies-literature
Project description:Colorectal cancer (CRC) is the third most common cancer in the word. Liver metastasis is the most common site of colorectal metastases. The prognosis of resectable colorectal liver metastases (CRLM) was improved in the recent years with the consideration of chemotherapy and surgical resection as part of the multidisciplinary management of the disease; the current 5-year survival rates after resection of liver metastases are 25% to 40%. Resectable synchronous or metachronous liver metastases should be treated with perioperative chemotherapy based on three months of FOLFOX4 (5-fluorouracil [5FU], folinic acid [LV], and oxaliplatin) chemotherapy before surgery and three months after surgery. In the case of primary surgery, pseudo-adjuvant chemotherapy for 6 months, based on 5FU/LV, FOLFOX4, XELOX (capecitabine and oxaliplatin) or FOLFIRI (5FU/LV and irinotecan), should be indicated. In potentially resectable disease, primary chemotherapy based on more intensive regimens such as FOLFIRINOX (5FU/LV, irinotecan and oxaliplatin) should be considered to enhance the chance of cure. The palliative chemotherapy based on FOLFIRI, or FOLFOX4/XELOX with or without targeted therapies, is the mainstay treatment of unresectable disease. This review would provide additional insight into the problem of optimal integration of chemotherapy and surgery in the management of CRLM.
| S-EPMC3251538 | biostudies-other
Project description:BackgroundColorectal cancer (CRC) is one of the most malignant gastrointestinal cancers worldwide. The liver is the most important metastatic target organ, and liver metastasis is the leading cause of death in patients with CRC. Owing to the lack of sensitive biomarkers and unclear molecular mechanism, the occurrence of liver metastases cannot be predicted and the clinical outcomes are bad for liver metastases. Therefore, it is very important to identify the diagnostic or prognostic markers for liver metastases of CRC.AimTo investigate the highly differentially expressed genes (HDEGs) and prognostic marker for liver metastases of CRC.MethodsData from three NCBI Gene Expression Omnibus (GEO) datasets were used to show HDEGs between liver metastases of CRC and tumour or normal samples. These significantly HDEGs of the three GEO datasets take the interactions. And these genes were screened through an online tool to explore the prognostic value. Then, TIMER and R package were utilized to investigate the immunity functions of the HDEGs and gene set enrichment analysis was used to explore their potential functions.ResultsBased on the selection criteria, three CRC datasets for exploration (GSE14297, GSE41258, and GSE49355) were chosen. Venn diagrams were used to show HDEGs common to the six groups and 47 HDEGs were obtained. The HDEGs were shown by using STRING and Cytoscape software. Based on the TCGA database, APOC1 showed significantly different expression between N2 and N0, and N2 and N1. And there was also a significant difference in expression between T2 and T4, and between T2 and T3. In 20 paired CRC and normal tissues, quantitative real-time polymerase chain reaction illustrated that the APOC1 mRNA was strongly upregulated in CRC tissues (P = 0.014). PrognoScan and GEPIA2 revealed the prognostic value of APOC1 for overall survival and disease-free survival in CRC (P < 0.05). TIMER showed that APOC1 has a close relationship with immune infiltration (P < 0.05).ConclusionAPOC1 is a biomarker that is associated with both the diagnosis and prognosis of liver metastases of CRC.
| S-EPMC8180235 | biostudies-literature