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

Publication ,  Journal Article
Chaudhary, R; Slebos, RJC; Noel, LC; Song, F; Poole, MI; Hoening, DS; Hernandez-Prera, JC; Conejo-Garcia, JR; Guevara-Patino, JA; Wang, X ...
Published in: Cancer Res Commun
May 2023

UNLABELLED: 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.

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Published In

Cancer Res Commun

DOI

EISSN

2767-9764

Publication Date

May 2023

Volume

3

Issue

5

Start / End Page

896 / 907

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Squamous Cell Carcinoma of Head and Neck
  • Hypoxia
  • Humans
  • Head and Neck Neoplasms
  • ErbB Receptors
  • Cetuximab
  • Carcinoma, Squamous Cell
  • CD8-Positive T-Lymphocytes
 

Citation

APA
Chicago
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MLA
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Chaudhary, R., Slebos, R. J. C., Noel, L. C., Song, F., Poole, M. I., Hoening, D. S., … Chung, C. H. (2023). EGFR Inhibition by Cetuximab Modulates Hypoxia and IFN Response Genes in Head and Neck Squamous Cell Carcinoma. Cancer Res Commun, 3(5), 896–907. https://doi.org/10.1158/2767-9764.CRC-22-0443
Chaudhary, Ritu, Robbert J. C. Slebos, Leenil C. Noel, Feifei Song, Maria I. Poole, Dirk S. Hoening, Juan C. Hernandez-Prera, et al. “EGFR Inhibition by Cetuximab Modulates Hypoxia and IFN Response Genes in Head and Neck Squamous Cell Carcinoma.Cancer Res Commun 3, no. 5 (May 2023): 896–907. https://doi.org/10.1158/2767-9764.CRC-22-0443.
Chaudhary R, Slebos RJC, Noel LC, Song F, Poole MI, Hoening DS, et al. EGFR Inhibition by Cetuximab Modulates Hypoxia and IFN Response Genes in Head and Neck Squamous Cell Carcinoma. Cancer Res Commun. 2023 May;3(5):896–907.
Chaudhary, Ritu, et al. “EGFR Inhibition by Cetuximab Modulates Hypoxia and IFN Response Genes in Head and Neck Squamous Cell Carcinoma.Cancer Res Commun, vol. 3, no. 5, May 2023, pp. 896–907. Pubmed, doi:10.1158/2767-9764.CRC-22-0443.
Chaudhary R, Slebos RJC, Noel LC, Song F, Poole MI, Hoening DS, Hernandez-Prera JC, Conejo-Garcia JR, Guevara-Patino JA, Wang X, Xie M, Tan AC, Chung CH. EGFR Inhibition by Cetuximab Modulates Hypoxia and IFN Response Genes in Head and Neck Squamous Cell Carcinoma. Cancer Res Commun. 2023 May;3(5):896–907.

Published In

Cancer Res Commun

DOI

EISSN

2767-9764

Publication Date

May 2023

Volume

3

Issue

5

Start / End Page

896 / 907

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Squamous Cell Carcinoma of Head and Neck
  • Hypoxia
  • Humans
  • Head and Neck Neoplasms
  • ErbB Receptors
  • Cetuximab
  • Carcinoma, Squamous Cell
  • CD8-Positive T-Lymphocytes