Crizotinib and ceritinib trigger immunogenic cell death via on-target effects

Adriana Petrazzuolo; Maria Perez-Lanzon; Peng Liu; M Chiara Maiuri; Guido Kroemer

doi:10.1080/2162402X.2021.1973197

Crizotinib and ceritinib trigger immunogenic cell death via on-target effects

Oncoimmunology. 2021 Oct 25;10(1):1973197. doi: 10.1080/2162402X.2021.1973197. eCollection 2021.

Authors

Adriana Petrazzuolo^{1

2}, Maria Perez-Lanzon^{1

2}, Peng Liu^{1

2}, M Chiara Maiuri^{1

2}, Guido Kroemer^{1

2

3}

Affiliations

¹ Team "Metabolism, Cancer & Immunity",Centre De Recherche Des Cordeliers, Inserm UMRS1138, Université De Paris, Sorbonne Université, Paris, France.
² Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
³ Pôle De Biologie, Hôpital Européen Georges Pompidou, ; Paris, France.

Abstract

Immunogenic cell death (ICD) has initially been discovered in the context of chemotherapy. High-dose crizotinib also stimulates ICD, as we described for non-small cell lung cancer lacking activating chromosomal aberrations of ALK or ROS1, the usual targets of crizotinib, indicating that crizotinib may act through off-target effects. However, we found that low-dose of ALK inhibitors, crizotinib and ceritinib, may stimulate ICD in anaplastic large cell lymphoma, in which ALK is activated due to a chromosomal translocation, suggesting on target ICD-promoting effects.

Keywords: ALK inhibitors; anaplastic large cell lymphoma; immunogenicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anaplastic Lymphoma Kinase / genetics
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Crizotinib / therapeutic use
Humans
Immunogenic Cell Death
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Pyrimidines
Sulfones

Substances

Proto-Oncogene Proteins
Pyrimidines
Sulfones
Crizotinib
Anaplastic Lymphoma Kinase
Protein-Tyrosine Kinases
ceritinib

Grants and funding

GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Fondation “ARC pour la recherche sur le cancer”; Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; the LabEx Immuno-Oncology (ANR-18-IDEX-0001); the RHU Torino Lumière; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and the SIRIC Cancer Research and Personalized Medicine (CARPEM). OK receives funding from the DIM elicit of the Ile de France. AP has been supported by European Union Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN-ETN) Grant, Award No.: 675712 and the Fondation “ARC pour la recherche sur le cancer”.