Cytokine deregulation in cancer

Endogenous cytokines are aberrantly produced in many cancers, and serve as autocrine growth factors or indicators in immune response to the tumors. Hence, cytokine deregulation is likely to participate in the development or evolution of the malignant process. Over the last few years, endogenous cytokine levels have been correlated with phenotypic manifestations of cancer and with prognosis. For instance, serum IL-6 levels are elevated in both relapsed and newly-diagnosed Hodgkin’s and non-Hodgkin’s lymphoma, and these levels correlate with established prognostic features. Furthermore, in diffuse large cell lymphoma, serum IL-6 level is an independent prognostic variable for both complete remission and failure-free survival. Serum IL-10 levels are also elevated in lymphoid malignancies and predict outcome. In some cases, it may be that the balance between endogenous cytokine agonists and antagonists is disrupted. For instance, in chronic myelogenous leukemia, high cellular (leukocyte) levels of IL-1 beta and low levels of IL-1 receptor antagonist (IL-1RA) are seen in advanced disease and correlate with reduced survival. The molecular mechanisms underlying cytokine deregulation are now being investigated, with preliminary data suggesting heterogeneous genetic driving forces, including oncogene aberrations and viral infection.