Targeting cytotoxic T-lymphocyte antigen 4 in immunotherapies for melanoma and other cancers.
The immune system can simultaneously protect against tumor growth and sculpt resistant tumor strains. By a variety of mechanisms, anti-cytotoxic T-lymphocyte antigen (CTLA)-4 therapy may shift such opposing forces towards tumor elimination. In recent clinical trials, anti-CTLA-4 therapy induces durable responses that correlate with markers of immune activity, such as antigen-specific CD4(+) or CD8(+) cytokine release, antitumor antibody formation or cellular phenotype differentiation. However, some patients exhibit atypical responses to anti-CTLA-4 therapy, demonstrating transient/delayed responses or heterogeneity by lesion site. Such atypical responses may offer insight into the mechanism of anti-CTLA-4 therapy. The immunogram - a newly described graphical synthesis of treatment data and immune correlates in individual patients - may help us to confirm, reject or formulate new hypotheses regarding the mechanism of anti-CTLA-4 activity.
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David B
DB
Melanoma/Sarcoma Service, Memorial Sloan-Kettering Cancer Center, NY, USA.
Yuan
Jianda
J
Wolchok
Jedd D
JD
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D060908:CTLA-4 Antigen; D003131:Combined Modality Therapy; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D007167:Immunotherapy / Q000379:methods*; D000074324:Ipilimumab; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011878:Radiotherapy / Q000379:methods
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007155:Immunologic Factors; D000074324:Ipilimumab