Abstract
Immunoprofiling has an established impact on the prognosis of several cancers; however, its role and definition in high-grade serous ovarian cancer (HGSOC) are mostly unknown. This study is to investigate immunoprofiling which could be a prognostic factor in HGSOC. We produced tumor microarrays of 187 patients diagnosed with HGSOC. We performed a multiplexed immunofluorescence staining using Opal Multiplex IHC kit and quantitative analysis with Vectra-Inform system. The expression intensities of programmed death-ligand 1 (PD-L1), CD4, CD8, CD20, FoxP3, and CK in whole tumor tissues were evaluated. The enrolled patients showed general characteristics, mostly FIGO stage III/IV and responsive to chemotherapy. Each immune marker showed diverse positive densities, and each tumor sample represented its immune characteristics as an inflamed tumor or noninflamed tumor. No marker was associated with survival as a single one. Interestingly, high ratios of CD8 to FoxP3 and CD8 to PD-L1 were related to the favorable overall survival (77 vs. 39 months, 84 vs. 47 months, respectively), and CD8 to PD-L1 ratio was also a significant prognostic factor (HR 0.621, 95% CI 0.420–0.917, p = 0.017) along with well-known clinical prognostic factors. Additionally, CD8 to PD-L1 ratio was found to be higher in the chemosensitive group (p = 0.034). In conclusion, the relative expression levels of CD8, FoxP3, and PD-L1 were significantly related to the clinical outcome of patients with HGSOC, which could be a kind of significant immunoprofiling of ovarian cancer patients to apply for treatment.
Highlights
Epithelial ovarian cancer (EOC) is the most fatal gynecologic cancer, which can be primarily attributed to acquired resistance to chemotherapy and late-stage diagnosis
We further demonstrated the association between the expression ratio of immune markers and response to chemotherapy and survival in patients with Highgrade serous ovarian cancer (HGSOC), suggesting that immunoprofiling would be a potent prognostic factor in ovarian cancer
We described that high ratios of CD8 to FoxP3 and CD8 to programmed death-ligand 1 (PD-L1) are significantly related to the overall survival, which is roughly twice as long (77 vs. 39 months, 84 vs. 47 months, respectively), and that CD8 to PD-L1 ratio is a significant favorable prognostic factor (HR 0.621, 95% CI: 0.420–0.917, p = 0.017) along with other clinical factors
Summary
Epithelial ovarian cancer (EOC) is the most fatal gynecologic cancer, which can be primarily attributed to acquired resistance to chemotherapy and late-stage diagnosis. Since the mid-2010s, a few new drugs have been introduced to the pool of approved chemotherapeutic agents, such as bevacizumab and olaparib [3,4]. To our disappointment, their benefit for overall survival is minimal at best in patients with relapsed EOC, so the worst prognosis of EOC among gynecologic cancers has not improved significantly over the decades [5,6]. A new, effective treatment strategy is urgently needed to overcome drug resistance while simultaneously preventing metastasis and cancer progression from reducing the survival of patients with EOC
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