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

卷:9

Eyad Elkord¹  Reem Saleh²  SalmanM. Toor²  RowaidaZ. Taha²  Varun Sasidharan Nair²  Khaled Murshed³  Mahmood Al-Dhaheri⁴  MohamedA. Kurer⁴  Mohamed Abu Nada⁴  AymanA. Ahmed⁴  Mahwish Khawar⁴ 

[1] Biomedical Research Center, School of Science, Engineering and Environment, University of Salford, Manchester M5 4WT, UK;

[2] Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar;

[3] Department of Pathology, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar;

[4] Department of Surgery, Hamad Medical Corporation, P.O. Box 3050 Doha, Qatar;

关键词: colorectal cancer;    tumor microenvironment;    T cells;    transcriptomics;   

DOI  :  10.3390/vaccines9040334

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown