Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4<sup>+</sup> 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
Affiliations
Salman M. Toor
Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar
Varun Sasidharan Nair
Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar
Reem Saleh
Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar
Rowaida Z. Taha
Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar
Khaled Murshed
Department of Pathology, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar
Mahmood Al-Dhaheri
Department of Surgery, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar
Mahwish Khawar
Department of Surgery, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar
Ayman A. Ahmed
Department of Surgery, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar
Mohamed A. Kurer
Department of Surgery, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar
Mohamed Abu Nada
Department of Surgery, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar
Eyad Elkord
Biomedical Research Center, School of Science, Engineering and Environment, University of Salford, Manchester M5 4WT, UK
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.
