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Transcriptomic Profiling of Tumor-Infiltrating CD4+TIM-3+ T Cells Reveals Their Suppressive, Exhausted, and Metastatic Characteristics in Colorectal Cancer Patients.
- Source :
- Vaccines; Mar2020, Vol. 8 Issue 1, p71, 1p
- Publication Year :
- 2020
-
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<superscript>+</superscript> 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<superscript>+</superscript> and CD3<superscript>+</superscript>CD4<superscript>−</superscript> (CD8<superscript>+</superscript>) TILs. CD4<superscript>+</superscript>TIM-3<superscript>+</superscript> TILs expressed higher levels of T regulatory cell (Tregs)-signature genes, including FoxP3 and Helios, compared with their TIM-3<superscript>−</superscript> 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<superscript>+</superscript>TIM-3<superscript>+</superscript> TILs, which could favor proliferation/invasion and induce inflammatory and T-cell exhaustion pathways. In addition, we found that CD4<superscript>+</superscript>TIM-3<superscript>+</superscript> TILs potentially support tumor invasion and metastasis, compared with conventional CD4<superscript>+</superscript>CD25<superscript>+</superscript> 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<superscript>+</superscript> TILs, which could improve their targeting in more specific therapeutic approaches in CRC patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2076393X
- Volume :
- 8
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Vaccines
- Publication Type :
- Academic Journal
- Accession number :
- 142496635
- Full Text :
- https://doi.org/10.3390/vaccines8010071