Immunological off-target effects of imatinib

Laurence Zitvogel; Sylvie Rusakiewicz; Bertrand Routy; Maha Ayyoub; Guido Kroemer

doi:10.1038/nrclinonc.2016.41

Immunological off-target effects of imatinib

Nat Rev Clin Oncol. 2016 Jul;13(7):431-46. doi: 10.1038/nrclinonc.2016.41. Epub 2016 Mar 31.

Authors

Laurence Zitvogel^{1

2}, Sylvie Rusakiewicz^{1

2}, Bertrand Routy^{1

2}, Maha Ayyoub^{1

2}, Guido Kroemer^{3

4

5}

Affiliations

¹ Gustave Roussy Cancer Campus (GRCC), INSERM U1015, 114 rue Edouard Vaillant, 94805 Villejuif, France.
² Center of Clinical Investigations in Biotherapies of Cancer, CICBT1428, GRCC, 94805 Villejuif, France.
³ 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.
⁴ Pôle de Biologie, Hôpital Européen Georges Pompidou, 75015 Paris, France.
⁵ Metabolomics and Cell Biology Platforms, GRCC, 94805 Villejuif, France.

PMID: 27030078
DOI: 10.1038/nrclinonc.2016.41

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.

Publication types

Review

MeSH terms

Antigens, Neoplasm / drug effects
Antigens, Neoplasm / immunology
Antineoplastic Agents / immunology*
Antineoplastic Agents / therapeutic use
B7 Antigens / drug effects
B7 Antigens / immunology
Drug Approval
Forecasting
Gastrointestinal Stromal Tumors / drug therapy
Gastrointestinal Stromal Tumors / immunology*
Hematopoiesis / drug effects
Hematopoiesis / immunology
Humans
Imatinib Mesylate / immunology*
Imatinib Mesylate / therapeutic use
Immune Tolerance / drug effects
Immune Tolerance / immunology
Immunity, Cellular / drug effects
Immunologic Surveillance / drug effects
Immunologic Surveillance / immunology
Killer Cells, Natural / drug effects
Killer Cells, Natural / immunology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
Molecular Chaperones / drug effects
Molecular Chaperones / immunology
Molecular Targeted Therapy / methods
Natural Cytotoxicity Triggering Receptor 3 / drug effects
Natural Cytotoxicity Triggering Receptor 3 / immunology
Protein-Tyrosine Kinases / drug effects
Protein-Tyrosine Kinases / immunology
T-Lymphocytes / drug effects
T-Lymphocytes / immunology
Tumor Escape / drug effects
Tumor Escape / immunology
Vascular Endothelial Growth Factor A / drug effects
Vascular Endothelial Growth Factor A / immunology

Substances

Antigens, Neoplasm
Antineoplastic Agents
B7 Antigens
BAG6 protein, human
Molecular Chaperones
NCR3 protein, human
NCR3LG1 protein, human
Natural Cytotoxicity Triggering Receptor 3
Vascular Endothelial Growth Factor A
Imatinib Mesylate
Protein-Tyrosine Kinases