Immune-active microenvironment in small cell carcinoma of the ovary, hypercalcemic type: Rationale for immune checkpoint blockade Journal Article
| Authors: | Jelinic, P.; Ricca, J.; Van Oudenhove, E.; Olvera, N.; Merghoub, T.; Levine, D. A.; Zamarin, D. |
| Article Title: | Immune-active microenvironment in small cell carcinoma of the ovary, hypercalcemic type: Rationale for immune checkpoint blockade |
| 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 (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. |
| Keywords: | pd-1; expression; lung-cancer; association; tumor-infiltrating lymphocytes; blockade; number; nivolumab; smarca4 mutations; neoantigen load; instable endometrial cancers |
| Journal Title: | JNCI: Journal of the National Cancer Institute |
| Volume: | 110 |
| Issue: | 7 |
| ISSN: | 0027-8874 |
| Publisher: | Oxford University Press |
| Date Published: | 2018-07-01 |
| Start Page: | 787 |
| End Page: | 790 |
| Language: | English |
| ACCESSION: | WOS:000445380200016 |
| DOI: | 10.1093/jnci/djx277 |
| PROVIDER: | wos |
| PMCID: | PMC6037122 |
| PUBMED: | 29365144 |
| Notes: | Article -- djx277 -- Source: Wos |
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