Cytokines regulate virtually aspects of innate and adaptive immunity, including the initiation, execution and extinction of tumor-targeting immune responses. Over the past three decades, the possibility of using recombinant cytokines as a means to elicit or boost clinically relevant anticancer immune responses has attracted considerable attention. However, only three cytokines have been approved so far by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, namely, recombinant interleukin (IL)-2 and two variants of recombinant interferon alpha 2 (IFN-α2a and IFN-α2b). Moreover, the use of these cytokines in the clinics is steadily decreasing, mostly as a consequence of: (1) the elevated pleiotropism of IL-2, IFN-α2a and IFN-α2b, resulting in multiple unwarranted effects; and (2) the development of highly effective immunostimulatory therapeutics, such as immune checkpoint blockers. Despite this and other obstacles, research in the field continues as alternative cytokines with restricted effects on specific cell populations are being evaluated. Here, we summarize research preclinical and clinical developments on the use of recombinant cytokines for immunostimulation in cancer patients.

Center of Clinical Investigations in Biotherapies of Cancer 1428 Villejuif France

Department of Medicine and Immunology Program Memorial Sloan Kettering Cancer Center New York NY

Department of Radiation Oncology Weill Cornell Medical College New York NY USA

Dept of Immunology 2nd Faculty of Medicine and University Hospital Motol Charles University Prague Czech Republic

Equipe 11 labellisée Ligue contre le Cancer Centre de Recherche des Cordeliers Paris France

Gustave Roussy Comprehensive Cancer Institute Villejuif France

Hematology and Oncology Department Hospital Universitario Morales Meseguer Murcia Spain

Immunoreceptors of the Innate and Adaptive System IDIBAPS Barcelona Spain

INSERM U1015 Villejuif France

INSERM U1138 Paris France

Karolinska Institute Department of Women's and Children's Health Karolinska University Hospital Stockholm Sweden

Metabolomics and Cell Biology Platforms Gustave Roussy Comprehensive Cancer Institute Villejuif France

Pôle de Biologie Hopitâl Européen George Pompidou AP HP Paris France

Sandra and Edward Meyer Cancer Center New York NY USA

Sotio Prague Czech Republic

Université Paris Descartes Paris 5 France

Université Paris Sud Paris XI Le Kremlin Bicêtre France

Université Pierre et Marie Curie Paris 6 Paris

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