Combination of Chemotherapy and Cytokine Therapy in Treatment of Cancers

MARIANA MALVICINI; MANGLIO RIZZO; LAURA ALANIZ; GUILLERMO MAZZOLINI

Cancer Immunology: Bench to Bedside Immunotherapy of Cancers

Springer

Lugar: N York; Año: 2015;

Increasing evidence suggests that immune responses participate in the control of cancer growth and that the immune system can be manipulated in different ways to recognize and attack tumors. Cytokines are proteins produced by monocytes, macrophages, and lymphocytes, which regulate proliferation, differentiation, and functional activation of immune cells, playing a key role in this response. A number of cytokines (e.g., interleukin (IL)-2, IL-4, IL-6, IL-7, IL-12, IL-15, and IL-18; granulocyte macrophage colony-stimulating factor (GM-CSF); granulocyte colony-stimulating factor (G-CSF); tumor necrosis factor (TNF)-α; macrophage colony-stimulating factor (MCSF or CSF-1); and interferon (IFN)-γ) demonstrated their ability to induce immunity against cancer. However, systemic administration of recombinant cytokines may induce unaffordable toxicity; in addition, the immunosuppressive milieu clearly limits its potential efficacy. In this context, protocols combining chemotherapy and immunotherapy with cytokines demonstrated potential for therapeutic synergy. For example, cyclophosphamide, gemcitabine, paclitaxel, and doxorubicin have been used for this purpose. Moreover, new studies indicate that reducing the dose of conventional chemotherapy could act in synergy to generate immunity against many tumors. This chapter provides an overview of the evidence that supports the rationale for the use of combined therapy as a strategy to achieve specific antitumoral immune response in cancer patients.