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10.3390/cells11182866
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Article

The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response

by
Justine De Azevedo
1,
Jana Mourtada
1,
Cyril Bour
1,2,
Véronique Devignot
1,
Philippe Schultz
1,3,
Christian Borel
1,4,
Erwan Pencreach
1,5,
Georg Mellitzer
1,
Christian Gaiddon
1,* and
Alain C. Jung
1,2,*
1
Laboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, France
2
Laboratoire de Biologie Tumorale, Institut de Cancérologie Strasbourg Europe, 67200 Strasbourg, France
3
Department of Otorhinolaryngology and Head and Neck Surgery, Hôpitaux Universitaires de Strasbourg, 67200 Strasbourg, France
4
Department of Medical Oncology, Institut de Cancérologie Strasbourg Europe, 67200 Strasbourg, France
5
Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, 67200 Strasbourg, France
*
Authors to whom correspondence should be addressed.
Cells 2022, 11(18), 2866; https://doi.org/10.3390/cells11182866
Submission received: 3 August 2022 / Revised: 9 September 2022 / Accepted: 12 September 2022 / Published: 14 September 2022
(This article belongs to the Special Issue Immunogenic Cell Stress and Death)
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Abstract

(1) Background: The first line of treatment for recurrent/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) has recently evolved with the approval of immunotherapies that target the anti-PD-1 immune checkpoint. However, only about 20% of the patients display a long-lasting objective tumor response. The modulation of cancer cell immunogenicity via a treatment-induced immunogenic cell death is proposed to potentially be able to improve the rate of patients who respond to immune checkpoint blocking immunotherapies. (2) Methods: Using human HNSCC cell line models and a mouse oral cancer syngeneic model, we have analyzed the ability of the EXTREME regimen (combination therapy using the anti-EGFR cetuximab antibody and platinum-based chemotherapy) to modify the immunogenicity of HNSCC cells. (3) Results: We showed that the combination of cetuximab and cisplatin reduces cell growth through both cell cycle inhibition and the induction of apoptotic cell death independently of p53. In addition, different components of the EXTREME regimen were found to induce, to a variable extent, and in a cell-dependent manner, the emission of mediators of immunogenic cell death, including calreticulin, HMGB1, and type I Interferon-responsive chemokines. Interestingly, cetuximab alone or combined with the IC50 dose of cisplatin can induce an antitumor immune response in vivo, but not when combined with a high dose of cisplatin. (4) Conclusions: Our observations suggest that the EXTREME protocol or cetuximab alone are capable, under conditions of moderate apoptosis induction, of eliciting the mobilization of the immune system and an anti-tumor immune response in HNSCC.
Keywords: head and neck squamous cell carcinoma; cetuximab; cisplatin; apoptosis; immunogenic cell death head and neck squamous cell carcinoma; cetuximab; cisplatin; apoptosis; immunogenic cell death

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MDPI and ACS Style

De Azevedo, J.; Mourtada, J.; Bour, C.; Devignot, V.; Schultz, P.; Borel, C.; Pencreach, E.; Mellitzer, G.; Gaiddon, C.; Jung, A.C. The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response. Cells 2022, 11, 2866. https://doi.org/10.3390/cells11182866

AMA Style

De Azevedo J, Mourtada J, Bour C, Devignot V, Schultz P, Borel C, Pencreach E, Mellitzer G, Gaiddon C, Jung AC. The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response. Cells. 2022; 11(18):2866. https://doi.org/10.3390/cells11182866

Chicago/Turabian Style

De Azevedo, Justine, Jana Mourtada, Cyril Bour, Véronique Devignot, Philippe Schultz, Christian Borel, Erwan Pencreach, Georg Mellitzer, Christian Gaiddon, and Alain C. Jung. 2022. "The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response" Cells 11, no. 18: 2866. https://doi.org/10.3390/cells11182866

APA Style

De Azevedo, J., Mourtada, J., Bour, C., Devignot, V., Schultz, P., Borel, C., Pencreach, E., Mellitzer, G., Gaiddon, C., & Jung, A. C. (2022). The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response. Cells, 11(18), 2866. https://doi.org/10.3390/cells11182866

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