| Autor: |
Cheng, Danni, Qiu, Ke, Li, Daibo, Mao, Minzi, Rao, Yufang, Song, Yao, Feng, Lan, Shao, Xiuli, Jiang, Chuanhuan, Wang, Yan, Li, Li, Chen, Xuemei, Wu, Sisi, Wang, Haiyang, Liu, Jun, Yu, Haopeng, Zhang, Wei, Chen, Fei, Zhao, Yu, Ren, Jianjun |
| Předmět: |
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| Zdroj: |
MedComm; Jun2024, Vol. 5 Issue 6, p1-16, 16p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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