EGFR Inhibition by Cetuximab Modulates Hypoxia and IFN Response Genes in Head and Neck Squamous Cell Carcinoma.

Autor:	Chaudhary R; Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida., Slebos RJC; Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida., Noel LC; Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida., Song F; Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida., Poole MI; Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida., Hoening DS; Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida., Hernandez-Prera JC; Department of Pathology, Moffitt Cancer Center, Tampa, Florida., Conejo-Garcia JR; Department of Immunology, Moffitt Cancer Center, Tampa, Florida., Guevara-Patino JA; Department of Immunology, Moffitt Cancer Center, Tampa, Florida., Wang X; Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida., Xie M; Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida., Tan AC; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., Chung CH; Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2023 May 22; Vol. 3 (5), pp. 896-907. Date of Electronic Publication: 2023 May 22 (Print Publication: 2023).
DOI:	10.1158/2767-9764.CRC-22-0443
Abstrakt:	Head and neck squamous cell carcinoma (HNSCC) has one of the most hypoxic and immunosuppressive tumor microenvironments (TME) among solid tumors. However, there is no proven therapeutic strategy to remodel the TME to be less hypoxic and proinflammatory. In this study, we classified tumors according to a Hypoxia-Immune signature, characterized the immune cells in each subgroup, and analyzed the signaling pathways to identify a potential therapeutic target that can remodel the TME. We confirmed that hypoxic tumors had significantly higher numbers of immunosuppressive cells, as evidenced by a lower ratio of CD8 + T cells to FOXP3 + regulatory T cells, compared with nonhypoxic tumors. Patients with hypoxic tumors had worse outcomes after treatment with pembrolizumab or nivolumab, anti-programmed cell death-1 inhibitors. Our expression analysis also indicated that hypoxic tumors predominantly increased the expression of the EGFR and TGFβ pathway genes. Cetuximab, an anti-EGFR inhibitor, decreased the expression of hypoxia signature genes, suggesting that it may alleviate the effects of hypoxia and remodel the TME to become more proinflammatory. Our study provides a rationale for treatment strategies combining EGFR-targeted agents and immunotherapy in the management of hypoxic HNSCC. Significance: While the hypoxic and immunosuppressive TME of HNSCC has been well described, comprehensive evaluation of the immune cell components and signaling pathways contributing to immunotherapy resistance has been poorly characterized. We further identified additional molecular determinants and potential therapeutic targets of the hypoxic TME to fully leverage currently available targeted therapies that can be administered with immunotherapy. (© 2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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