Sasidharan Nair, V, Toor, SM, Taha, RZ, Ahmed, AA, Kurer, MA, Murshed, K, Soofi, ME, Ouararhni, K, Alajez, NM, Abu Nada, M and Elkord, E 2020, 'Transcriptomic profiling of tumor-infiltrating CD4 + TIM-3 + T Cells reveals their suppressive, exhausted, and metastatic characteristics in colorectal cancer patients' , Vaccines, 8 (1) , e71.
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Abstract
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.
| Item Type: | Article |
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| Additional Information: | ** From MDPI via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2076-393X **History: published 06-02-2020; accepted 04-02-2020 |
| Uncontrolled Keywords: | colorectal cancer, tumor microenvironment, T cell immunoglobulin mucin-3, exhausted T cells, metastasis |
| Schools: | Schools > School of Environment and Life Sciences > Biomedical Research Centre |
| Journal or Publication Title: | Vaccines |
| Publisher: | MDPI |
| ISSN: | 2076-393X |
| Related URLs: | |
| Funders: | Qatar Foundation |
| SWORD Depositor: | Publications Router |
| Depositing User: | Publications Router |
| Date Deposited: | 10 Feb 2020 10:33 |
| Last Modified: | 10 Feb 2020 10:45 |
| URI: | http://usir.salford.ac.uk/id/eprint/56393 |
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