Article ; Online: Deciphering the immune landscape of head and neck squamous cell carcinoma: A single-cell transcriptomic analysis of regulatory T cell responses to PD-1 blockade therapy.
2023 Volume 18, Issue 12, Page(s) e0295863
Abstract: Immunotherapy is changing the Head and Neck Squamous Cell Carcinoma (HNSCC) landscape and improving outcomes for patients with recurrent or metastatic HNSCC. A deeper understanding of the tumor microenvironment (TME) is required in light of the ... ...
| Abstract | Immunotherapy is changing the Head and Neck Squamous Cell Carcinoma (HNSCC) landscape and improving outcomes for patients with recurrent or metastatic HNSCC. A deeper understanding of the tumor microenvironment (TME) is required in light of the limitations of patients' responses to immunotherapy. Here, we aimed to examine how Nivolumab affects infiltrating Tregs in the HNSCC TME. We used single-cell RNA sequencing data from eight tissues isolated from four HNSCC donors before and after Nivolumab treatment. Interestingly, the study found that Treg counts and suppressive activity increased following Nivolumab therapy. We also discovered that changes in the CD44-SSP1 axis, NKG2C/D-HLA-E axis, and KRAS signaling may have contributed to the increase in Treg numbers. Furthermore, our study suggests that decreasing the activity of the KRAS and Notch signaling pathways, and increasing FOXP3, CTLA-4, LAG-3, and GZMA expression, may be mechanisms that enhance the killing and suppressive capacity of Tregs. Additionally, the result of pseudo-temporal analysis of the HNSCC TME indicated that after Nivolumab therapy, the expression of certain inhibitory immune checkpoints including TIGIT, ENTPD1, and CD276 and LY9, were decreased in Tregs, while LAG-3 showed an increased expression level. The study also found that Tregs had a dense communication network with cluster two, and that certain ligand-receptor pairs, including SPP1/CD44, HLA-E/KLRC2, HLA-E/KLRK1, ANXA1/FPR3, and CXCL9/FCGR2A, had notable changes after the therapy. These changes in gene expression and cell interactions may have implications for the role of Tregs in the TME and in response to Nivolumab therapy. |
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| MeSH term(s) | Humans ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Squamous Cell Carcinoma of Head and Neck/genetics ; Squamous Cell Carcinoma of Head and Neck/metabolism ; T-Lymphocytes, Regulatory ; Programmed Cell Death 1 Receptor/metabolism ; Nivolumab/pharmacology ; Nivolumab/therapeutic use ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/metabolism ; Proto-Oncogene Proteins p21(ras)/metabolism ; Gene Expression Profiling ; Tumor Microenvironment ; B7 Antigens ; NK Cell Lectin-Like Receptor Subfamily C/metabolism |
| Chemical Substances | Programmed Cell Death 1 Receptor ; Nivolumab (31YO63LBSN) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; CD276 protein, human ; B7 Antigens ; KLRC2 protein, human ; NK Cell Lectin-Like Receptor Subfamily C |
| Language | English |
| Publishing date | 2023-12-14 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2267670-3 |
| ISSN | 1932-6203 ; 1932-6203 |
| ISSN (online) | 1932-6203 |
| ISSN | 1932-6203 |
| DOI | 10.1371/journal.pone.0295863 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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