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

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Vaccines
• Subjects: colorectal cancer; tumor microenvironment; T cells; transcriptomics
• Online Access: https://www.mdpi.com/2076-393X/9/4/334

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.