| Autor: |
Danni Cheng, Ke Qiu, Daibo Li, Minzi Mao, Yufang Rao, Yao Song, Lan Feng, Xiuli Shao, Chuanhuan Jiang, Yan Wang, Li Li, Xuemei Chen, Sisi Wu, Haiyang Wang, Jun Liu, Haopeng Yu, Wei Zhang, Fei Chen, Yu Zhao, Jianjun Ren |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
MedComm, Vol 5, Iss 6, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2688-2663 |
| DOI: |
10.1002/mco2.572 |
| Popis: |
Abstract Tumor‐infiltrating CD4+ T cells orchestrate the adaptive immune response through remarkable plasticity, and the expression patterns of exhaustion‐related inhibitory receptors in these cells differ significantly from those of CD8+ T cells. Thus, a better understanding of the molecular basis of CD4+ T cell exhaustion and their responses to immune checkpoint blockade (ICB) is required. Here, we integrated multiomics approaches to define the phenotypic and molecular profiles of exhausted CD4+ T cells in oropharyngeal squamous cell carcinoma (OPSCC). Two distinct immune‐promoting (Module 1) and immunosuppressive (Module 2) functional modules in tumor‐infiltrating CD4+ T cells were identified, and both the immune‐promoting function of Module 1 cells and immunosuppressive function of Module 2 cells were positively associated with their corresponding exhaustion states. Furthermore, the application of ICBs targeting effector CD4+ T cells in Module 1 (αPD‐1) and Treg cells in Module 2 (αCTLA‐4) in mouse models could help reinvigorate the effector function of Module 1‐exhausted CD4+ T cells and reduce the immunosuppressive function of Module 2‐exhausted CD4+ T cells, ultimately promoting OPSCC tumor regression. Taken together, our study provides a crucial cellular basis for the selection of optimal ICB in treating OPSCC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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