Abstract
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a highly aggressive monogenic cancer driven by SMARCA4 mutations. Here, we report responses to anti-PD1 immunotherapy in four patients and characterize the immune landscape of SCCOHT tumors using quantitative immunofluorescence and gene expression profiling. Unexpectedly for a low mutation burden cancer, the majority of the tumors (eight of 11 cases) demonstrated PD-L1 expression with strong associated T-cell infiltration (R2 = 0.60-0.95). PD-L1 expression was detected in both tumor and stromal cells, with macrophages being the most abundant PD-L1-positive cells in some tumors (three of 11 cases). Transcriptional profiling revealed increased expression of genes related to Th1 and cytotoxic cell function in PD-L1-high tumors, suggesting that PD-L1 acts as a pathway of adaptive immune resistance in SCCOHT. These findings suggest that although SCCOHT are low-mutational burden tumors, their immunogenic microenvironment resembles the landscape of tumors that respond well to treatment with PD-1/PD-L1 blockade.
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adolescent
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Adult
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Antibodies, Monoclonal / therapeutic use*
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B7-H1 Antigen / antagonists & inhibitors
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B7-H1 Antigen / immunology
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Carcinoma, Small Cell / drug therapy*
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Carcinoma, Small Cell / genetics
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Carcinoma, Small Cell / immunology*
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Carcinoma, Small Cell / pathology
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Cell Cycle Checkpoints / drug effects
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Cell Cycle Checkpoints / immunology
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DNA Helicases / genetics
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Female
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Humans
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Hypercalcemia* / complications
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Hypercalcemia* / genetics
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Hypercalcemia* / immunology
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Hypercalcemia* / pathology
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Immunotherapy / methods
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Mutation
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Nuclear Proteins / genetics
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / immunology*
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Ovarian Neoplasms / pathology
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Programmed Cell Death 1 Receptor / antagonists & inhibitors
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Programmed Cell Death 1 Receptor / immunology
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Rationalization
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Transcription Factors / genetics
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Tumor Microenvironment / drug effects
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Tumor Microenvironment / immunology*
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Young Adult
Substances
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Antibodies, Monoclonal
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B7-H1 Antigen
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CD274 protein, human
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Nuclear Proteins
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PDCD1 protein, human
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Programmed Cell Death 1 Receptor
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Transcription Factors
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SMARCA4 protein, human
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DNA Helicases