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PLoS One. 2013 Oct 22;8(10):e76829. doi: 10.1371/journal.pone.0076829. eCollection 2013.

Natural killer T cells in advanced melanoma patients treated with tremelimumab.

Author information

1
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.

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.

PMID:
24167550
PMCID:
PMC3805549
DOI:
10.1371/journal.pone.0076829
[Indexed for MEDLINE]
Free PMC Article

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