Cytokines, Interferons, and Hematopoietic Growth Factors

Abstract

Overview Cytokines are a diverse family of signaling molecules encompassing interleukins, interferons, and hematopoietic growth factors. As important mediators of immune responses, cytokines play critical roles and have clinical relevance in cancer. Interleukins have numerous diverse effects in cancer, including influencing the growth, differentiation, or survival of endothelial cells; attracting inflammatory cell types or induce secondary cytokines to regulate angiogenesis; influencing the tumor environment and infiltrating hematopoietic effector cells; inhibiting or stimulating tumor growth; and regulating immune responses. Various immunostimulatory cytokines, including ILs, are administered to patients in an attempt to initiate or augment antitumor immune responses. Interferons are a large family of multifunctional secreted proteins involved in antiviral defense, cell growth regulation, and immune activation. The three types of IFNs, types I, II, and III, signal via specific cell surface receptors and the JAK‐STAT pathway to transcriptionally activate IFN‐regulated genes (IRGs). Alterations in IRG expression result in modulation of receptors for other cytokines, concentration of regulatory proteins on the surface of immune effector cells, and activation of enzymes that control cellular growth and function. Both natural and recombinant IFNs have shown antitumor activity as single agents in more than a dozen malignancies. Hematopoietic growth factors, most notably epoetin, thrombopoietin, and granulocyte colony‐stimulating factor (G‐CSF), are used in the clinic to stimulate the growth and differentiation of red blood cells, platelets, or neutrophils in clinical settings including after chemotherapy or bone marrow transplantation in a restorative role.