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; Sasidharan Nair, V; Saleh, R; Taha, RZ; Murshed, K; Al-Dhaheri, M; Khawar, M; Ahmed, AA; Kurer, MA; Abu Nada, M; Elkord, E

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.

Citation

Toor, S., Sasidharan Nair, V., Saleh, R., Taha, R., Murshed, K., Al-Dhaheri, M., …Elkord, E. (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. https://doi.org/10.3390/vaccines9040334

• Journal Article Type: Article
• Acceptance Date: Mar 26, 2021
• Publication Date: Apr 1, 2021
• Deposit Date: Apr 15, 2021
• Publicly Available Date: Apr 15, 2021
• Journal: Vaccines
• Publisher: MDPI
• Volume: 9
• Issue: 4
• Pages: e334
• DOI: https://doi.org/10.3390/vaccines9040334
• Publisher URL: https://doi.org/10.3390/vaccines9040334
• Related Public URLs: https://www.mdpi.com/journal/vaccines
• Additional Information: 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; Funders : Qatar Foundation; Grant Number: VR04