Immune‐related gene expression signatures: A step forward in the stratification of patients with ovarian clear cell carcinoma†

Clear cell carcinoma of the ovary (CCC) is one of the five major histological types of ovarian cancer and presents specific clinicopathological features, such as a higher prevalence in Asian population and a poor response to conventional chemotherapy. In a recent publication in The Journal of Pathology, Heong and coworkers demonstrated the heterogeneity of the immune landscape of CCC. They reported the immune signatures observed in a large cohort of CCC, including tumours from both Asian and Caucasian women. The authors analysed three cohorts from Europe, Japan and Singapore with a total of 246 tumours, and evaluated 730 immune related genes using NanoString technology. The study revealed four main transcriptional subtypes characterised by the expression of specific sets of genes: PD1-high (11%), CTLA4-high (29%), antigen-presentation (42%), and a pro-angiogenic subtype (18%). The two main conclusions of the study are: 1) CCC in women of Asian and Caucasian descent share significant molecular similarities, since all four molecular signatures are present in all the cohorts analysed, without any evident differences in frequency; and 2) the PD1-high and CTLA4-high subtypes were associated with worse clinical outcomes and may be useful when stratifying treatment in early-stage tumours. The immune signature could represent a promising biomarker of immunotherapy response if future prospective studies confirm it.

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