Molecular and transcriptional basis of bidirectional CD4+ T cell exhaustion in oropharyngeal squamous cell carcinoma
In: MedComm, Jg. 5 (2024), Heft 6, S. n/a-n/a
Online
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Zugriff:
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.
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Molecular and transcriptional basis of bidirectional CD4+ T cell exhaustion in oropharyngeal squamous cell carcinoma
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Autor/in / Beteiligte Person: | 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 |
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Zeitschrift: | MedComm, Jg. 5 (2024), Heft 6, S. n/a-n/a |
Veröffentlichung: | Wiley, 2024 |
Medientyp: | academicJournal |
ISSN: | 2688-2663 (print) |
DOI: | 10.1002/mco2.572 |
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