National Cancer Institute, Vilnius, Lithuania.
Baltic Institute of Advanced Technology, Vilnius, Lithuania.
Am J Reprod Immunol. 2020 Jul;84(1):e13244. doi: 10.1111/aji.13244. Epub 2020 May 9.
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.
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.
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.
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.
目前的肿瘤免疫学范式强调了肿瘤免疫微环境的作用，并区分了几种组织学和转录上不同的免疫肿瘤亚型。然而，这种分类的实验验证迄今为止仅限于选定的癌症类型。在这里，我们旨在探索卵巢癌中是否存在炎症型、排除型和荒漠型免疫亚型，并研究它们与疾病结局的关联。
我们使用了来自癌症基因组图谱的公开卵巢癌数据集来开发亚型分配算法，然后在已知肿瘤亚型的 32 名真实患者队列中对其进行了验证。
我们使用了公开数据集的 489 名卵巢癌患者的临床和基因表达数据，确定了三个转录上不同的簇，代表炎症型、排除型和荒漠型亚型。我们开发了一种两步式分型算法，COL5A2 作为分离排除型肿瘤的标志物，CD2、TAP1 和 ICOS 用于区分炎症型和荒漠型肿瘤。基于基因表达的分型算法在真实世界队列中的准确性为 75%。此外，我们还证实，患有炎症型肿瘤的患者更有可能存活更长时间。
我们的研究结果强调了卵巢肿瘤中存在转录和组织学上不同的免疫亚型，并强调了免疫分型作为治疗个体化的临床工具的潜在益处。
