The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Tim-3 Expression Defines Regulatory T Cells in Human Tumors
Open accessAbstract
Tim-3, a member of the novel Tim (T cell immunoglobulin and mucin domain) family, has been reported to negatively regulate the immune responses against viral infection and had implications for autoimmune disease. However, the nature and role of Tim-3(+) CD4 T cells in human tumors remain largely unknown. In the present study, we characterized Tim-3(+) CD4 T cells in 100 specimens from human hepatocellular, cervical, colorectal and ovarian carcinoma patients. Compared with peripheral blood and nontumor-infiltrating lymphocytes, the lymphocytes isolated from the corresponding tumor tissues of hepatocellular, cervical, colorectal and ovarian carcinoma patients contained significantly greater proportion of Tim-3(+) CD4 T cells. The majority of tumor-derived Tim-3(+) CD4 T cells exhibited an impaired capacity to produce IFN-γ and IL-2, but expressed higher levels of CD25, Foxp3, CTLA-4 and GITR than their Tim-3(-) CD4 T cell counterparts. In contrast, most Tim-3(+) CD4 T cells isolated from the paired nontumor tissues and peripheral blood did not express these molecules. Moreover, tumor-derived Tim-3(+) CD4 T cells, but not tumor-derived Tim-3(-) CD4 T cells, significantly suppressed the proliferation of autologous CD8(+) T cells in vitro. Notably, multi-color immunofluorescence and confocal microscopy demonstrated that Tim-3(+)Foxp3(+)CD4(+) cells were preferentially distributed in the tumor nest rather than the peritumoral stroma of hepatocellular carcinoma. Together, our data indicate that Tim-3-expressing CD4 T cells in human tumors could represent the functional regulatory T cells which contribute to the formation of the immune-suppressive tumor micromilieu.
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Cites
PD-1 and Its Ligands in Tolerance and Immunity
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“The frequency of Tim-3 CD4 T cells was also significantly higher among CD25 or CD127 cells than their CD25(2) or CD127 counterparts (Figure 3A and S5); these characteristics are also shared by human Treg cells [30,36-38].”
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Cited by
Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation
Anderson, A. C., Joller, N., & Kuchroo, V. K. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.001 · Cited by 2,096
TIM3 comes of age as an inhibitory receptor
Wolf, Y., Anderson, A. C., & Kuchroo, V. K. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0224-6 · Cited by 959
Tim‐3 and its role in regulating anti‐tumor immunity
Das, M., Zhu, C., & Kuchroo, V. K. (2017) · Immunological Reviews · doi:10.1111/imr.12520 · Cited by 856
Yang, R., Sun, L., Li, C.-F., Wang, Y.-H., Yao, J., Li, H., Yan, M., Chang, W.-C., Hsu, J.-M., Cha, J.-H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21099-2 · Cited by 632
Cardiovascular toxicities associated with immune checkpoint inhibitors
Hu, J.-R., Florido, R., Lipson, E. J., Naidoo, J., Ardehali, R., Tocchetti, C. G., Lyon, A. R., Padera, R. F., Johnson, D. B., & Moslehi, J. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz026 · Cited by 508
Metadata
- Authors
- Yan, J., Zhang, Y., Zhang, J.-P., Liang, J., Li, L., & Zheng, L.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-03-05
- Volume
- 8
- Issue
- 3
- Pages
- e58006
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2056211666
- Cited by
- 182
- References
- 9
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- gold
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