title: Natural killer T cells in advanced melanoma patients treated with tremelimumab.
abstract: A significant barrier to effective immune clearance of cancer is loss of antitumor cytotoxic T cell activity. Antibodies to block pro-apoptotic/downmodulatory signals to T cells are currently being tested. Because invariant natural killer T cells (iNKT) can regulate the balance of Th1/Th2 cellular immune responses, we characterized the frequencies of circulating iNKT cell subsets in 21 patients with melanoma who received the anti-CTLA4 monoclonal antibody tremelimumab alone and 8 patients who received the antibody in combination with MART-126-35 peptide-pulsed dendritic cells (MART-1/DC). Blood T cell phenotypes and functionality were characterized by flow cytometry before and after treatment. iNKT cells exhibited the central memory phenotype and showed polyfunctional cytokine production. In the combination treatment group, high frequencies of pro-inflammatory Th1 iNKT CD8(+) cells correlated with positive clinical responses. These results indicate that iNKT cells play a critical role in regulating effective antitumor T cell activity.
authors.affiliation: Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America ; UCLA AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Ibarrondo
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: Thinle
authors.initials: T
authors.lastname: Chodon
authors.forename: Earl
authors.initials: E
authors.lastname: Avramis
authors.forename: Yohan
authors.initials: Y
authors.lastname: Lee
authors.forename: Hooman
authors.initials: H
authors.lastname: Sazegar
authors.forename: Jason
authors.initials: J
authors.lastname: Jalil
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.forename: Richard C
authors.initials: RC
authors.lastname: Koya
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schmid
authors.forename: Jesus
authors.initials: J
authors.lastname: Gomez-Navarro
authors.forename: Beth D
authors.initials: BD
authors.lastname: Jamieson
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: Begoña
authors.initials: B
authors.lastname: Comin-Anduix
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D058965:MART-1 Antigen / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D058965:MART-1 Antigen; C520704:tremelimumab