The biology of interleukin-2 efficacy in the treatment of patients with renal cell carcinoma.
Renal cell carcinoma (RCC) is the eighth most common malignancy in adults in the United States. More than 50% of individuals present with metastatic disease and conventional chemotherapeutic strategies have been associated with poor response rates. Immunotherapy with Interleukin (IL)-2, however, induces durable remission, achieving >10 year recurrence free survival in 5-10% of patients with advanced RCC. First described as a T cell growth factor, IL-2 has a wide spectrum of effects in the immune system. Some of the possible mechanisms by which IL-2 carries out its anticancer effects include the augmentation of cytotoxic immune cell functions and reversal of T cell anergy, enabling delivery of immune cells and possibly serum components into tumor. IL-2 indirectly limits tumor escape mechanisms such as defective tumor cell expression of Class I or Class II molecules or expansion of regulatory T cells. Indirect effects on the tumor microenvironment are also likely and associated with rather dramatic T cell infiltration during the global delayed type hypersensitivity response that is associated with systemic IL-2 administration. The IL-2 signaling pathway, its effects on immune cells, and its role in various independent mechanisms of tumor surveillance likely play a role but little substantive data defining a clear phenotype or genotype of IL-2 responders distinguishing them from nonresponders has emerged in the last 25 years since IL-2 therapy was initiated. At best, we can only speculate that the disturbed homeostatic host/tumor interaction is reset in a small subset of patients allowing an antitumor response to recover or ensue.
Romo de Vivar Chavez
Antonio
A
Department of Surgery, University of Pittsburgh, G.27A Hillman Cancer Center 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
de Vera
Michael E
ME
Liang
Xiaoyan
X
Lotze
Michael T
MT
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
D000970:Antineoplastic Agents; D007376:Interleukin-2