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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Article number334
JournalVaccines
Volume9
Issue number4
DOIs
Publication statusPublished - 2021
Externally publishedYes

Keywords

  • Colorectal cancer
  • T cells
  • Transcriptomics
  • Tumor microenvironment

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