Interleukin-2 mastering regulation in cancer and autoimmunity.
Autoimmunity and tumor immunity evolved as two distinct arenas in immunological research. However, the identification of self-antigens as the major components of malignant cells may define a central role for autoimmunity in cancer control tuned by peripheral immunoregulatory mechanisms avoiding self-aggression. Emerging evidence documents a triple antagonistic role of interleukin-2 (IL-2) in vivo promoting survival, apoptosis, and the generation of regulatory T cells. We have found that IL-2 administration reduces the clinical course of experimental autoimmune encephalomyelitis and enhances immunoregulation in tumor-bearing mice. However, actively induced anti-IL-2 antibodies restore the response to nominal antigens in tumor-induced immunosuppressed host and induced therapeutic effect in transplantable and chemically induced tumors. It is suggested that IL-2 may contribute dynamically to the maintenance of natural immunological tolerance, preventing pathological autoimmunity, but may affect antitumor immunity. Cancer research has gained from autoimmunity understanding that tumor escape strategies include the natural mechanisms of immune tolerance and the ways to imbalance the peripheral regulatory mechanisms. Interestingly, therapeutic manipulations of immunoregulation have limited antitumor effects, although promoting collaterally infrequent autoimmune diseases. It may suggest that tumors may reinforce tolerance to protect themselves from the immune attack, a process that may involve dynamically various mechanisms including IL-2. Understanding this acquired experience from tumors may help utilize them to revert the immunopathology in autoimmune diseases.
Montero
Enrique
E
Center of Molecular Immunology, Experimental Immunotherapy Department, 216 and 15, Playa, P.O. Box: 16040, Havana 11600, Cuba. enrique@cim.sld.cu
Alonso
Livan
L
Perez
Rolando
R
Lage
Agustin
A
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology