A gene signature for immune subtyping of desert, excluded, and inflamed ovarian tumors.

Problem: The current tumor immunology paradigm emphasizes the role of the immune tumor microenvironment and distinguishes several histologically and transcriptionally different immune tumor subtypes. However, the experimental validation of such classification is so far limited to selected cancer types. Here, we aimed to explore the existence of inflamed, excluded, and desert immune subtypes in ovarian cancer, as well as investigate their association with the disease outcome.

Method Of Study: We used the publicly available ovarian cancer dataset from The Cancer Genome Atlas for developing subtype assignment algorithm, which was next verified in a cohort of 32 real-world patients of a known tumor subtype.

Results: Using clinical and gene expression data of 489 ovarian cancer patients in the publicly available dataset, we identified three transcriptionally distinct clusters, representing inflamed, excluded, and desert subtypes. We developed a two-step subtyping algorithm with COL5A2 serving as a marker for separating excluded tumors, and CD2, TAP1, and ICOS for distinguishing between inflamed and desert tumors. The accuracy of gene expression-based subtyping algorithm in a real-world cohort was 75%. Additionally, we confirmed that patients bearing inflamed tumors are more likely to survive longer.

Conclusion: Our results highlight the presence of transcriptionally and histologically distinct immune subtypes among ovarian tumors and emphasize the potential benefit of immune subtyping as a clinical tool for treatment tailoring.