Contrasting Roles of IL-2 and IL-15 in the Life and Death of Lymphocytes: Implications for Immunotherapy

Abstract

IL-2 has been approved for use in the treatment of patients with metastatic renal cell carcinoma or with metastatic melanoma. It has also been used as a component of vaccines for cancer. However, due to its pivotal role in AICD it may lead to the death of T cells that recognize antigens expressed on the tumor cells. That is, these cells may interpret the tumor cells as self. Futhermore, the inhibition mediated by IL-2 on the survival of memory T cells directed toward the tumor is not desired. Thus, IL-15 with its inhibitory action on AICD and its stimulatory role in the persistence of memory CD8+ T cells may be superior to IL-2 in the treatment of cancer and as a component of vaccines directed toward cancer or infectious agents.In conclusion, our emerging understanding of the IL-2/IL-2R and IL-15/IL-15R systems including the definition of the actions that these cytokines share as well as those functions where their roles are distinct opens new possibilities for the development of more rational immune intervention that may be of value in the prevention of allograft rejection, in the treatment of lymphocytic leukemia/lymphoma, diseases associated with the retrovirus HTLV-I, as well as T cell–mediated autoimmune disorders.Oppenhimer-Marks Brezinschek Mohamadzadeh Vita Lipsky 1998xOppenhimer-Marks, N., Brezinschek, R.I., Mohamadzadeh, M., Vita, R., and Lipsky, P.E. J. Clin. Invest. 1998; 101: 1261–1272CrossRef | PubMedSee all ReferencesOppenhimer-Marks Brezinschek Mohamadzadeh Vita Lipsky 1998