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

Salman M Toor; Varun Sasidharan Nair; Reem Saleh; Rowaida Z Taha; Khaled Murshed; Mahmood Al-Dhaheri; Mahwish Khawar; Ayman A Ahmed; Mohamed A Kurer; Mohamed Abu Nada; Eyad Elkord

doi:10.3390/vaccines9040334

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 (Basel). 2021 Apr 1;9(4):334. doi: 10.3390/vaccines9040334.

Affiliations

¹ Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar.
² Department of Pathology, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar.
³ Department of Surgery, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar.
⁴ Biomedical Research Center, School of Science, Engineering and Environment, University of Salford, Manchester M5 4WT, UK.

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.

Keywords: T cells; colorectal cancer; transcriptomics; tumor microenvironment.

Grants and funding

VR04/Qatar Foundation