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- Title
Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4 + T Cells Associated with Poor Disease-Specific Survival.
- Authors
Toor, Salman M.; Sasidharan Nair, Varun; Saleh, Reem; Taha, Rowaida Z.; Murshed, Khaled; Al-Dhaheri, Mahmood; Khawar, Mahwish; Ahmed, Ayman A.; Kurer, Mohamed A.; Abu Nada, Mohamed; Elkord, Eyad; Tripp, Ralph A.; Bruno, Antonino
- Abstract
Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4+ T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4+ with CD8+ TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4+ TILs. The top 200 deregulated genes in CD4+ TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in the TCGA dataset and were used to calculate "poor prognosis score" (ppScore), which was significantly associated with disease-specific survival. High ppScore patients showed lower expression of Treg-, Th1-, and Th17-related genes, and higher expression of Th2-related genes. Our data highlight the significance of T cells within the TME and identify a unique candidate prognostic gene signature for CD4+ TILs in CRC patients.
- Subjects
COLORECTAL cancer; T cells; CYTOTOXIC T cells; CANCER cells; CANCER patients
- Publication
Vaccines, 2021, Vol 9, Issue 4, p334
- ISSN
2076-393X
- Publication type
Article
- DOI
10.3390/vaccines9040334