Serum soluble interleukin 2 receptor alpha in human cancer of adults and children: a review

Abstract

Cancer growth and development is associated with the stimulation of the innate immune system, including enhanced interleukin 2 receptor (IL-2R) expression in immune cells and its shedding into the circulation in a soluble form of sIL-2Ralpha. In most haematological malignancies, including different types of leukaemias and lymphomas, sIL-2Ralpha has been found to be released directly from the surface of neoplastic cells thus reflecting the tumour bulk, turnover and activity. Several studies have proved that not only lymphoid cancer cells, but also some non-lymphoid cancer cells, express IL-2R on their surface. They include malignant melanoma and carcinomas of the kidney, head and neck, oesophagus and lung. It is suggested that in most malignant solid tumours, elevated levels of sIL-2Ralpha are likely to be the product of normal peripheral mononuclear cells activated in response to the neoplasm's growth or that they are released from activated lymphoid cells infiltrating neoplastic tissues. This latter hypothesis has been proved by discovering the high expression of CD25 on the cell surface of most of these cells. Although the precise source and biological role of sIL-2Ralpha has not been clarified definitively, pretreatment serum levels of sIL-2Ralpha have been shown to reflect the activity, advancement and biological aggressiveness of many types of cancer in adults and children as well as to correlate with prognosis and overall survival. The possibility of enriching the diagnostic tools of oncologists with a new biochemical marker of activity of neoplasms resulted in numerous studies and reports concerning the clinical usefulness of sIL-2Ralpha measurements in adult and, less frequently, in paediatric malignancies. This article presents the actual knowledge concerning the structure, source and biological function of sIL-2Ralpha in patients with haematological and non-haematological malignancies. The authors review the published data on clinical applicability of soluble IL-2Ralpha determination in terms of diagnostics, prognosis and treatment monitoring of particular types of malignant disorders both in adults and in children. They also provide an insight into the clinical usefulness of sLL-2Ralpha-blocking antibodies in patients with cancer, and in those who reject organ transplants, develop graft-versus-host disease after allogeneic bone marrow transplantation and are affected with autoimmune disorders.