title: Immunological off-target effects of imatinib.
abstract: Around 15 years ago, imatinib mesylate (Gleevec(®) or Glivec(®), Novartis, Switzerland) became the very first 'targeted' anticancer drug to be clinically approved. This drug constitutes the quintessential example of a successful precision medicine that has truly changed the fate of patients with Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours by targeting the oncogenic drivers of these diseases, BCR-ABL1 and KIT and/or PDGFR, mutations in which lead to gain of function of tyrosine kinase activities. Nonetheless, the aforementioned paradigm might not fully explain the clinical success of this agent in these diseases. Growing evidence indicates that the immune system has a major role both in determining the therapeutic efficacy of imatinib (and other targeted agents) and in restraining the emergence of escape mutations. In this Review, we re-evaluate the therapeutic utility of imatinib in the context of the anticancer immunosurveillance system, and we discuss how this concept might inform on novel combination regimens that include imatinib with immunotherapies.
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), INSERM U1015, 114 rue Edouard Vaillant, 94805 Villejuif, France.|Center of Clinical Investigations in Biotherapies of Cancer, CICBT1428, GRCC, 94805 Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), INSERM U1015, 114 rue Edouard Vaillant, 94805 Villejuif, France.|Center of Clinical Investigations in Biotherapies of Cancer, CICBT1428, GRCC, 94805 Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), INSERM U1015, 114 rue Edouard Vaillant, 94805 Villejuif, France.|Center of Clinical Investigations in Biotherapies of Cancer, CICBT1428, GRCC, 94805 Villejuif, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Routy
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), INSERM U1015, 114 rue Edouard Vaillant, 94805 Villejuif, France.|Center of Clinical Investigations in Biotherapies of Cancer, CICBT1428, GRCC, 94805 Villejuif, France.
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.affiliation: Equipe 11 labelisée par la Ligue Nationale contre le Cancer, INSERM U1138, Centre de Recherche des Cordeliers, University of Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.|Pôle de Biologie, Hôpital Européen Georges Pompidou, 75015 Paris, France.|Metabolomics and Cell Biology Platforms, GRCC, 94805 Villejuif, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000951:Antigens, Neoplasm / Q000187:drug effects / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use; D060887:B7 Antigens / Q000187:drug effects / Q000276:immunology; D017277:Drug Approval; D005544:Forecasting; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000276:immunology*; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D000068877:Imatinib Mesylate / Q000276:immunology* / Q000627:therapeutic use; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D007157:Immunologic Surveillance / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000276:immunology*; D018832:Molecular Chaperones / Q000187:drug effects / Q000276:immunology; D058990:Molecular Targeted Therapy / Q000379:methods; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000187:drug effects / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019139:Tumor Escape / Q000187:drug effects / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D060887:B7 Antigens; C092009:BAG6 protein, human; D018832:Molecular Chaperones; C431710:NCR3 protein, human; C542363:NCR3LG1 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D042461:Vascular Endothelial Growth Factor A; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases