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

Toor, SM ORCID: https://orcid.org/0000-0002-4683-3329, Sasidharan Nair, V, Saleh, R, Taha, RZ ORCID: https://orcid.org/0000-0001-6119-8389, Murshed, K ORCID: https://orcid.org/0000-0001-8045-363X, Al-Dhaheri, M, Khawar, M, Ahmed, AA, Kurer, MA, Abu Nada, M and Elkord, E ORCID: https://orcid.org/0000-0002-3868-0318 2021, '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' , Vaccines, 9 (4) , e334.

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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.

Item Type: Article
Additional Information: ** From MDPI via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2076-393X **History: published 01-04-2021; accepted 26-03-2021
Schools: Schools > School of Environment and Life Sciences
Journal or Publication Title: Vaccines
Publisher: MDPI
ISSN: 2076-393X
Related URLs:
Funders: Qatar Foundation
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 15 Apr 2021 13:08
Last Modified: 28 Aug 2021 10:54
URI: http://usir.salford.ac.uk/id/eprint/59997

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