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Immune-Active Microenvironment in Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Rationale for Immune
Petar Jelinic1, Jacob Ricca2,3, Elke Van Oudenhove1
1Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY.
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.
Insights
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) shows PD-L1 expression and T-cell infiltration, suggesting potential response to immunotherapy. These findings highlight the immunogenic microenvironment of SCCOHT tumors.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive cancer primarily driven by SMARCA4 mutations.
- Understanding the tumor immune microenvironment is crucial for developing effective therapies.
Observation:
- This study investigated the immune landscape of SCCOHT tumors and patient responses to anti-PD1 immunotherapy.
- Quantitative immunofluorescence and gene expression profiling were employed to characterize tumor-infiltrating immune cells and PD-L1 expression.
Findings:
- Despite a low mutation burden, most SCCOHT tumors (8/11) exhibited PD-L1 expression, correlating with significant T-cell infiltration.
- PD-L1 expression was observed on both tumor and stromal cells, notably on macrophages in some cases.
- PD-L1-high tumors showed increased expression of genes associated with Th1 and cytotoxic cell functions, indicating adaptive immune resistance.
Implications:
- The findings suggest that SCCOHT tumors possess an immunogenic microenvironment that may respond favorably to PD-1/PD-L1 blockade immunotherapy.
- This research opens avenues for exploring immunotherapy as a treatment strategy for SCCOHT, even in the context of low mutational burden.
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