The role of interleukin-2 receptor alpha in cancer

Abstract

Interleukin-2 (IL-2) is the major growth factor for activated T-lymphocytes and stimulates clonal expansion and maturation of these lymphocytes. IL-2 binds to its receptor complex, IL-2Ralpha, beta, and gamma chains, and exerts its effect via second messengers, mainly tyrosine kinases, which ultimately stimulate gene expression. The heterotrimerization of the receptor chains leads to high affinity binding for IL-2. The functional importance of IL-2Ralpha in hematopoietic cell systems is well known. However, the potential role that IL-2Ralpha plays in tumorigenesis is still not fully elucidated. Il-2Ralpha expression has been found in many types of cancers, including leukemia, lymphoma, lung, breast, head-and-neck and prostate. Recent evidence shows that high expression of IL-2Ralpha in tumors correlates with a poor prognosis for the patient. This review details the current known functions of IL-2Ralpha in cancer cells and some of the therapies used to combat IL-2Ralpha-mediated cell signaling.

Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: Association with asymptomatic inflammatory prostatitis NIH category IV

“…The data concerning the prevalence of grade IV prostatitis in patients with prostate cancer and BPH have been published previously [25]. High expression of IL-2R in tumour tissue is obviously associated with a poorer prognosis of the disease for the patient [13]. Patients with B-cell lymphoma and high sIL-2R levels in serum had a significantly poorer prognosis [32].…”

“…These initiate the production of interleukin, interferon and tumour necrosis factor-, and stimulate the proliferation of cytotoxic cells and lymphokine-activated killer cells, as well as the cytotoxicity of macrophages. IL-2 is referred to as a T-cell growth factor [12][13][14][15]. The regulatory T lymphocytes CD8 + and CD25 + , activated by IL-2, are found in prostate cancer tissue.…”

The Shared and Contrasting Roles of IL2 and IL15 in the Life and Death of Normal and Neoplastic Lymphocytes: Implications for Cancer Therapy

“…The scientific basis for this is that IL2Rα is not expressed by resting cells other than Tregs and CD56 hi CD16 lo NK cells but is constitutively expressed by an array of malignant cells of various T- and B-cell leukemias as well as T cells involved in select autoimmune disorders and those that participate in organ allograft rejection (56, 59). One form of IL2 receptor-directed therapy involves the use of unarmed antibodies specific for IL2Rα including basiliximab (Simulect: Novartis AG) and daclizumab (also known as anti-Tac, Zenapax), the first humanized antibody that was approved by the FDA (56, 58, 60, 61).…”

IL-2 and IFN-gamma in the retina of diabetic rats

“…IL-2 induces cell growth and differentiation with augmentation of cellular activities, and it may directly affect its target cells, or indirectly induce the expression of endogenous cytokines, such as INF-g [24]. Augmented concentrations of IL-2 and IFN-g in serum and other body fluids occur in diseases of neoplastic, infective, or autoimmune nature [25,26], but to our knowledge it has not been investigated in relationship to diabetic retinopathy. Earlier studies have only reported increased levels of the soluble receptors for IL-2 in serum [27,28] and in epiretinal membranes [10] from eyes of patients with proliferative diabetic retinopathy; however, neither IL-2 nor IFN-g increases in the retinal tissue during experimental diabetic retinopathy have been reported so far.…”