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
(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 res...
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MDPI AG
2022-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/18/2866 |
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| author | Justine De Azevedo Jana Mourtada Cyril Bour Véronique Devignot Philippe Schultz Christian Borel Erwan Pencreach Georg Mellitzer Christian Gaiddon Alain C. Jung |
| author_facet | Justine De Azevedo Jana Mourtada Cyril Bour Véronique Devignot Philippe Schultz Christian Borel Erwan Pencreach Georg Mellitzer Christian Gaiddon Alain C. Jung |
| author_sort | Justine De Azevedo |
| collection | DOAJ |
| description | (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 IC<sub>50</sub> 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. |
| first_indexed | 2024-03-10T00:26:31Z |
| format | Article |
| id | doaj.art-44a521a4cd23489a8063ed49c377a312 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:26:31Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-44a521a4cd23489a8063ed49c377a3122023-11-23T15:33:32ZengMDPI AGCells2073-44092022-09-011118286610.3390/cells11182866The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune ResponseJustine De Azevedo0Jana Mourtada1Cyril Bour2Véronique Devignot3Philippe Schultz4Christian Borel5Erwan Pencreach6Georg Mellitzer7Christian Gaiddon8Alain C. Jung9Laboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, FranceLaboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, FranceLaboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, FranceLaboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, FranceLaboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, FranceLaboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, FranceLaboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, FranceLaboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, FranceLaboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, FranceLaboratory Streinth, Université de Strasbourg-Inserm, UMR_S 1113 IRFAC, 67200 Strasbourg, France(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 IC<sub>50</sub> 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.https://www.mdpi.com/2073-4409/11/18/2866head and neck squamous cell carcinomacetuximabcisplatinapoptosisimmunogenic cell death |
| spellingShingle | Justine De Azevedo Jana Mourtada Cyril Bour Véronique Devignot Philippe Schultz Christian Borel Erwan Pencreach Georg Mellitzer Christian Gaiddon Alain C. Jung 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 head and neck squamous cell carcinoma cetuximab cisplatin apoptosis immunogenic cell death |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | extreme regimen associating cetuximab and cisplatin favors head and neck cancer cell death and immunogenicity with the induction of an anti cancer immune response |
| topic | head and neck squamous cell carcinoma cetuximab cisplatin apoptosis immunogenic cell death |
| url | https://www.mdpi.com/2073-4409/11/18/2866 |
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