New insights of common gamma chain in hematological malignancies

The common gamma chain (γc) receptor family of cytokines including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 has the common feature of sharing γc signaling subunit of their receptors. The γc cytokines have unique biological effects that regulate differentiation, survival and activation of multiple lymphocyte lineages and control proliferation of malignant cell by influencing tumor environment. It has been also described that different types of lymphoid leukemia and lymphoma exhibit expression of divergent γc cytokines and their receptors, as they may promote malignant transformation of lymphoid cells or on the contrary lead to tumor regression by inducing cell-cycle arrest. Therefore, cytokine-based or cytokine-directed blockade in cancer immunotherapy has currently revolutionized the development of cancer treatment. In this review, we will discuss about the role of γc cytokines and their signaling pathways in hematological malignancies and also propose a novel alternative approach that regulates γc cytokine responsiveness by γc in hematological malignancies.