Journal
BLOOD
Volume 126, Issue 22, Pages 2475-2478Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2015-03-632919
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Funding
- Public Health Service/Department of Health and Human Services grants - National Institutes of Health National Cancer Institute (NCI) National Clinical Trials Network [CA1800888, CA1800819, CA180801, CA180826, CA180846, CA180830, CA180858]
- NCI Community Oncology Research Program [CA189853, CA189953]
- NCI [A106802, CA135110]
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Blockade of immune checkpoints (ICPs) has led to impressive responses in cancer patients. However, the impact of preexisting immunity and ICPs on the risk of malignant transformation in human preneoplasia has not been prospectively studied. We prospectively analyzed antigen-specific BIT-cell immunity, immune composition of the tumor microenvironment, and the expression of a panel of ICPs on tumor and tumor-infiltrating immune cells in 305 patients with asymptomatic monoclonal gammopathy enrolled in S0120 under the auspices of SWOG. T-cell immunity against stem-cell antigen SOX2 and preserved humoral responses at study entry independently correlated with reduced risk of progression to clinical myeloma. Among the ICPs analyzed, expression of programmed death-ligand 1 (PD-L1) on tumor and infiltrating T cells correlated with increased risk of clinical malignancy, and blockade of this pathway boosted anti-SOX2 immunity in culture. These data suggest that stem-cell antigens and PD-L1 may be targeted for immunoprevention of myeloma.
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