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

<p dir="ltr">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<sup>+</sup&g...

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Main Author: Salman M. Toor (8854751) (author)
Other Authors: Varun Sasidharan Nair (5396393) (author), Reem Saleh (3513056) (author), Rowaida Z. Taha (8854754) (author), Khaled Murshed (8309781) (author), Mahmood Al-Dhaheri (9621035) (author), Mahwish Khawar (9621038) (author), Ayman A. Ahmed (18513762) (author), Mohamed A. Kurer (18513765) (author), Mohamed Abu Nada (8309784) (author), Eyad Elkord (5396390) (author)
Published: 2021
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Summary:<p dir="ltr">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<sup>+</sup> T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4<sup>+</sup> and CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4<sup>+</sup> with CD8<sup>+</sup> 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<sup>+</sup> TILs. The top 200 deregulated genes in CD4<sup>+</sup> 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<sup>+</sup> TILs in CRC patients.</p><p><br></p><h2>Other Information</h2><p dir="ltr">Published in: Vaccines<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/vaccines9040334" target="_blank">https://dx.doi.org/10.3390/vaccines9040334</a></p>