Genetic Mutations of Tim-3 Ligand and Exhausted Tim-3+ CD8+ T Cells and Survival in Diffuse Large B Cell Lymphoma
Joint Authors
Meng, Bin
Song, Zheng
Zhou, Shiyong
Jiao, Lei
He, Jin
Zhang, Tingting
Zhang, Zhenzhen
Ren, Tianyuan
Qiu, Lihua
Li, Lanfang
Zhai, Qiongli
Qian, Zhengzi
Wang, Xianhuo
Zhang, Huilai
Liu, Xianming
Zhao, Jing
Ren, Xiubao
Source
Journal of Immunology Research
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-10-30
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Tim-3 is a promising target for antitumor immunotherapy.
A number of clinical trials are evaluating the efficacy of anti-Tim-3 therapies as a single agent or combinations in solid tumors and haematologic malignancies.
However, there remains a considerable lack of data on Tim-3 signalling, especially the genetic characteristics and immune microenvironment, in diffuse large B cell lymphoma (DLBCL).
Herein, we identified three genetic mutations in galectin-9, a major ligand of Tim-3, in six patients with DLBCL (6/188, 3.2%) that were not detected in the COSMIC database.
The Oncomine database showed that the mRNA levels of Tim-3 were higher in DLBCL cells than those in normal B cells.
Multiplexed immunofluorescence revealed that patients with Tim-3-expressing tumor-infiltrating lymphocytes (Tim-3+ TILs) exhibited poor outcomes than those with Tim-3- TILs (p=0.041).
The median survival times of these patients were 65.0 (95% confidence interval (CI): 71.2–88.6) and 79.9 months (95% CI: 54.4–75.6), respectively.
Furthermore, we defined a novel subtype of exhausted T cells, named as exhausted Tim-3+ CD8+ T cells, and found that patients with exhausted Tim-3+ CD8+ T cells (median survival, 62.8 months, 95% CI: 50.0–75.6) exhibited shorter survival than those with nonexhausted Tim-3- CD8+ T cells (median survival, 82.5 months, 95% CI: 72.0–92.9; p=0.034).
Overall, these findings provide the genetic status of the Tim-3 ligand in DLBCL.
Patients with Tim-3+ TILs and exhausted Tim-3+ CD8+ T cells exhibited inferior survival, thus highlighting the possibility of potential therapeutic applications of the inhibition of Tim-3 alone or in combination with other immune checkpoints for treatment of patients with DLBCL.
American Psychological Association (APA)
Zhang, Tingting& Ren, Tianyuan& Song, Zheng& Zhao, Jing& Jiao, Lei& Zhang, Zhenzhen…[et al.]. 2020. Genetic Mutations of Tim-3 Ligand and Exhausted Tim-3+ CD8+ T Cells and Survival in Diffuse Large B Cell Lymphoma. Journal of Immunology Research،Vol. 2020, no. 2020, pp.1-9.
https://search.emarefa.net/detail/BIM-1187412
Modern Language Association (MLA)
Zhang, Tingting…[et al.]. Genetic Mutations of Tim-3 Ligand and Exhausted Tim-3+ CD8+ T Cells and Survival in Diffuse Large B Cell Lymphoma. Journal of Immunology Research No. 2020 (2020), pp.1-9.
https://search.emarefa.net/detail/BIM-1187412
American Medical Association (AMA)
Zhang, Tingting& Ren, Tianyuan& Song, Zheng& Zhao, Jing& Jiao, Lei& Zhang, Zhenzhen…[et al.]. Genetic Mutations of Tim-3 Ligand and Exhausted Tim-3+ CD8+ T Cells and Survival in Diffuse Large B Cell Lymphoma. Journal of Immunology Research. 2020. Vol. 2020, no. 2020, pp.1-9.
https://search.emarefa.net/detail/BIM-1187412
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1187412