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- Title
Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs.
- Authors
Raymond M. Wong; Ron R. Scotland; Roy L. Lau; Changyu Wang; Alan J. Korman; W. M. Kast; Jeffrey S. Weber
- Abstract
Negative co-stimulatory signaling mediated via cell surface programmed death (PD)-1 expression modulates T and B cell activation and is involved in maintaining peripheral tolerance. In this study, we examined the effects of a fully human PD-1-abrogating antibody on the in vitro expansion and function of human vaccine-induced CD8+ T cells (CTLs) specific for the melanoma-associated antigens glycoprotein 100 (gp100) and melanoma antigen recognized by T cells (MART)-1. PD-1 blockade during peptide stimulation augmented the absolute numbers of CD3+, CD4+, CD8+ and gp100/MART-1 MHC:peptide tetramer+ CTLs. This correlated with increased frequencies of IFN-γ-secreting antigen-specific cells and augmented lysis of gp100+/MART-1+ melanoma targets. PD-1 blockade also increased the fraction of antigen-specific CTLs that recognized melanoma targets by degranulation, suggesting increased recognition efficiency for cognate peptide. The increased frequencies and absolute numbers of antigen-specific CTLs by PD-1 blockade resulted from augmented proliferation, not decreased apoptosis. Kinetic analysis of cytokine secretion demonstrated that PD-1 blockade increased both type-1 and type-2 cytokine accumulation in culture without any apparent skewing of the cytokine repertoire. These findings have implications for developing new cancer immunotherapy strategies.
- Subjects
ANTIGENS; CELL membranes; GLYCOPROTEINS; CANCER immunotherapy; THERAPEUTICS
- Publication
International Immunology, 2007, Vol 19, Issue 10, p1223
- ISSN
0953-8178
- Publication type
Article
- DOI
10.1093/intimm/dxm091