4.6 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

期刊

CELLS
卷 11, 期 18, 页码 -

出版社

MDPI
DOI: 10.3390/cells11182866

关键词

head and neck squamous cell carcinoma; cetuximab; cisplatin; apoptosis; immunogenic cell death

资金

  1. Centre National pour la Recherche Scientifique (CNRS, France)
  2. Conference de Coordination Interregionale Grand Est-Bourgogne Franche-Comte de la Ligue Contre le Cancer
  3. Institut de cancerologie Strasbourg Europe
  4. Association pour la Recherche sur le Cancer
  5. ITMO Cancer
  6. European action COST Proteocure
  7. Interdisciplinary thematic Institute InnoVec
  8. IDEX Excellence grant from Unistra
  9. Institut National du Cancer
  10. Ministere de l'Enseignement Superieur et de la Recherche
  11. French national Ligue Contre le Cancer

向作者/读者索取更多资源

The EXTREME protocol or cetuximab alone are capable of eliciting an anti-tumor immune response in HNSCC under conditions of moderate apoptosis induction.
(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.

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