PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer

abstract

 Highlights

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Expression of PD-L1 in ovarian cancer was revaluated using modern antibody reagents

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PD-L1 expression positively correlated with tumor infiltrating lymphocytes

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PD-L1 expression was a favorable prognostic feature of high grade serous cancer

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Abstract

Objective

As a negative regulator of T cells, Programmed Death Ligand 1 (PD-L1) is both an indicator and inhibitor of anti-tumor immune responses, which has led to confusion about its prognostic significance. We investigated the primary source of PD-L1 expression in epithelial ovarian cancer and its relationship to tumor-infiltrating lymphocytes (TIL) and associated gene products.

Methods

Tissue microarrays containing high-grade serous carcinomas (HGSC) and endometrioid, clear cell and mucinous ovarian cancers from optimally debulked patients were assessed by immunohistochemistry for expression of PD-L1 and other markers (CD68, CD3, CD8, PD-1, CD103, FoxP3 and CD25). The Cancer Genome Atlas was interrogated for associations between PD-L1 expression and immune-related transcriptional and genomic features of HGSC.

Conclusions

PD-L1 is primarily expressed by macrophages in ovarian cancer and is strongly associated with both cytolytic and regulatory TIL subsets, resulting in a net positive association with survival. Tumors containing PD-L1⁺ macrophages appear caught in an immunological stalemate that may require multi-pronged immunotherapy to alleviate.