Manara - Qatar Research Repository
Browse
1/1
2 files

Transcriptomic Profiling of Tumor-Infiltrating CD4+TIM-3+ T Cells Reveals Their Suppressive, Exhausted, and Metastatic Characteristics in Colorectal Cancer Patients

journal contribution
submitted on 2024-06-10, 12:02 and posted on 2024-06-11, 09:32 authored by Varun Sasidharan Nair, Salman M Toor, Rowaida Z Taha, Ayman A Ahmed, Mohamed A Kurer, Khaled Murshed, Madiha E Soofi, Khalid Ouararhni, Nehad M. Alajez, Mohamed Abu Nada, Eyad Elkord

T cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint identified as one of the key players in regulating T-cell responses. Studies have shown that TIM-3 is upregulated in the tumor microenvironment (TME). However, the precise role of TIM-3 in colorectal cancer (CRC) TME is yet to be elucidated. We performed phenotypic and molecular characterization of TIM-3+ T cells in the TME and circulation of CRC patients by analyzing tumor tissues (TT, TILs), normal tissues (NT, NILs), and peripheral blood mononuclear cells (PBMC). TIM-3 was upregulated on both CD4+ and CD3+CD4 (CD8+) TILs. CD4+TIM-3+ TILs expressed higher levels of T regulatory cell (Tregs)-signature genes, including FoxP3 and Helios, compared with their TIM-3− counterparts. Transcriptomic and ingenuity pathway analyses showed that TIM-3 potentially activates inflammatory and tumor metastatic pathways. Moreover, NF-κB-mediated transcription factors were upregulated in CD4+TIM-3+ TILs, which could favor proliferation/invasion and induce inflammatory and T-cell exhaustion pathways. In addition, we found that CD4+TIM-3+ TILs potentially support tumor invasion and metastasis, compared with conventional CD4+CD25+ Tregs in the CRC TME. However, functional studies are warranted to support these findings. In conclusion, this study discloses some of the functional pathways of TIM-3+ TILs, which could improve their targeting in more specific therapeutic approaches in CRC patients.

Other Information

Published in: Vaccines
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3390/vaccines8010071

Funding

Open Access funding provided by the Qatar National Library.

Qatar Biomedical Research Institute, Qatar Foundation for Eyad Elkord (VR04).

History

Language

  • English

Publisher

MDPI

Publication Year

  • 2020

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • Cancer Research Center - QBRI
  • Hamad Medical Corporation
  • Hamad General Hospital - HMC