Immune-Active Microenvironment in Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Rationale for Immune Checkpoint Blockade

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 g...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute Vol. 110; no. 7; p. 787
Main Authors: Jelinic, Petar, Ricca, Jacob, Van Oudenhove, Elke, Olvera, Narciso, Merghoub, Taha, Levine, Douglas A, Zamarin, Dmitriy
Format: Journal Article
Language:English
Published: United States 01.07.2018
Subjects:
Adolescent
Adult
Antibodies, Monoclonal - therapeutic use
B7-H1 Antigen - antagonists & inhibitors
B7-H1 Antigen - immunology
Carcinoma, Small Cell - drug therapy
Carcinoma, Small Cell - genetics
Carcinoma, Small Cell - immunology
Carcinoma, Small Cell - pathology
Cell Cycle Checkpoints - drug effects
Cell Cycle Checkpoints - immunology
DNA Helicases - genetics
Female
Humans
Hypercalcemia - complications
Hypercalcemia - genetics
Hypercalcemia - immunology
Hypercalcemia - pathology
Immunotherapy - methods
Mutation
Nuclear Proteins - genetics
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - genetics
Ovarian Neoplasms - immunology
Ovarian Neoplasms - pathology
Programmed Cell Death 1 Receptor - antagonists & inhibitors
Programmed Cell Death 1 Receptor - immunology
Rationalization
Transcription Factors - genetics
Tumor Microenvironment - drug effects
Tumor Microenvironment - immunology
Young Adult
ISSN:1460-2105, 1460-2105
Online Access:Get more information
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Summary: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.
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ISSN:1460-2105
1460-2105
DOI:10.1093/jnci/djx277