Cytokines in cancer immunotherapy

Abstract

Cytokines are molecular messengers that allow the cells of the immune system to communicate with one another to generate a coordinated, robust, but self-limited response to a target antigen. The growing interest over the past two decades in harnessing the immune system to eradicate cancer has been accompanied by heightened efforts to characterize cytokines and exploit their vast signaling networks to develop cancer treatments. The goal of this paper is to review the major cytokines involved in cancer immunotherapy and discuss their basic biology and clinical applications. The paper will also describe new cytokines in pre-clinical development, combinations of biological agents, novel delivery mechanisms, and potential directions for future investigation using cytokines.

Figure 1.

Structural diagram of the major cytokine receptor families. Note that related receptors share common signaling chains and biologic activity is related to the presence of cytokine-binding chains, spatial orientation of the receptor complex and the temporal and cellular pattern of receptor expression. The physiologic impact of receptor signaling is summarized in Table 1. Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Immunology 2009 [4].

Figure 2.

Structural differences in IL-2 and IL-15 signaling. IL-2 and IL-15 bind two common subunits (IL-2R/15Rβ and γ_c) which signal through the same JAK and STAT molecules, accounting for the similarity in their actions. However, while IL-2 is a secreted cytokine and binds receptors on the surface of activated cells, IL-15 is primarily membrane bound and must be presented through cell-cell contact, which then involves additional costimulatory signals that further modify the cell response. Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Immunology, 2006 [104].