期刊
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
卷 110, 期 7, 页码 787-790出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djx277
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资金
- Katie Oppo Research Fund
- US Department of Defense Consortium Award [W81XWH-11-2-0230]
- NIH [P30 CA008748, P30 CA016087]
- Small Cell Ovarian Cancer Foundation
- Ovarian Cancer Research Foundation
- MSKCC Cycle for Survival
- US Department of Defense Ovarian Cancer Academy [W81XWH-16-1-0298]
- NATIONAL CANCER INSTITUTE [P30CA016087] Funding Source: NIH RePORTER
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 (R-2 = 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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