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Cytokines are pleiotropic soluble proteins used by immune cells to orchestrate a coordinated response against pathogens and malignancies. In cancer immunotherapy, cytokine-based drugs can be developed potentiating pro-inflammatory cytokines or blocking immunosuppressive cytokines. However, the complexity of the mechanisms of action of cytokines requires the use of biotechnological strategies to minimize systemic toxicity, while potentiating the antitumor response. Sequence mutagenesis, fusion proteins and gene therapy strategies are employed to enhance the half-life in circulation, target the desired bioactivity to the tumor microenvironment, and to optimize the therapeutic window of cytokines. In this review, we provide an overview of the different strategies currently being pursued in pre-clinical and clinical studies to make the most of cytokines for cancer immunotherapy.

Original publication




Journal article


International review of cell and molecular biology

Publication Date





107 - 141


Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IDISNA), Pamplona, Spain.


Humans, Neoplasms, Cytokines, Immunotherapy, Tumor Microenvironment