1. Single-cell characterization of infiltrating T cells identifies novel targets for gallbladder cancer immunotherapy.
- Author
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Zhang Y, Zuo C, Li Y, Liu L, Yang B, Xia J, Cui J, Xu K, Wu X, Gong W, and Liu Y
- Subjects
- Humans, T-Lymphocytes, Regulatory pathology, Immunotherapy, Macrophages pathology, Tumor Microenvironment, CD8-Positive T-Lymphocytes metabolism, Gallbladder Neoplasms genetics, Gallbladder Neoplasms therapy, Gallbladder Neoplasms metabolism
- Abstract
Gallbladder cancer (GBC) is among the most common malignancies of biliary tract system due to its limited treatments. The immunotherapeutic targets for T cells are appealing, however, heterogeneity of T cells hinds its further development. We systematically construct T cell atlas by single-cell RNA sequencing; and utilized the identified gene signatures of high_CNV_T cells to predict molecular subtyping towards personalized therapeutic treatments for GBC. We identified 12 T cell subtypes, where exhausted CD8
+ T cells, activated/exhausted CD8+ T cells, and regulatory T cells were predominant in tumors. There appeared to be an inverse relationship between Th17 and Treg populations with Th17 levels significantly reduced, whereas Tregs were concomitantly increased. Furthermore, we first established subtyping criterion to identify three subtypes of GBC based on their pro-tumorigenic microenvironments, e.g., the type 1 group shows more M2 macrophages infiltration, while the type 2 group is infiltrated by highly exhausted CD8+ T cells, B cells and Tregs with suppressive activities. Our study provides valuable insights into T cell heterogeneity and suggests that molecular subtyping based on T cells might provide a potential immunotherapeutic strategy to improve GBC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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