Focus on FOCIS: interleukin 2 treatment associated autoimmunity.
A patient from the University of Pittsburgh is presented who developed autoimmunity during IL-2 based combination therapy. IL-2 was originally described as a "T cell growth factor" capable of expanding previously activated T cells, enhancing the cytotoxicity of antigen-specific cytotoxic T cells and NK cells. High dose Interleukin 2 (HDIL2) is now FDA-approved for therapy of patients with metastatic melanoma and renal cell carcinoma, based on its ability to induce durable responses in 5-10% of patients. The antitumor effect of HDIL2 is incompletely understood, but it appears that this regimen alters the balance of immigrant T effector cells in relation to T suppressor cells. It promotes a less immunosuppressive tumor microenvironment, inducing tumor regression in a subset of patients that is yet to be defined. The antitumor activity of IL-2, as for other agents that promote durable antitumor activity against melanoma such as interferon alpha and anti-CTLA4 antibody, is frequently associated with development of autoimmunity as observed in this patient. We present studies investigating the mechanisms for the therapeutic benefit of HDIL2 in melanoma.
Moschos
Stergios J
SJ
University of Pittsburgh Federation of Clinical Immunologic Societies Center of Excellence, Pittsburgh, Pennsylvania 15213-1683, USA. moschossj@upmc.edu
Mandic
Maja
M
Kirkwood
John M
JM
Storkus
Walter J
WJ
Lotze
Michael T
MT
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D000077204:Temozolomide; D014820:Vitiligo / Q000139:chemically induced / Q000276:immunology
D007376:Interleukin-2; D003606:Dacarbazine; D000077204:Temozolomide