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.
Co-SPIONs are not cytotoxic to cancer cells, at least when used at a concentration of up to 0.95μg/mL. Co-SPIONs have a dose-dependent effect on the clonogenic potential and ESA marker expression in A2780 cells. Magnetic detection of low concentrations of Co-SPIONS in cancer cells is a promising tool for further applications of these nanoparticles in cancer diagnosis and treatment; however, extensive research in this field is needed.
The management of advanced ovarian cancer is challenging due to the high frequency of recurrence, often associated with the development of resistance to platinum-based chemotherapy. Molecular analyses revealed the complexity of ovarian cancer with particular emphasis on the immune system, which may contribute to disease progression and response to treatment. Cytokines and chemokines mediate the cross-talk between cancer and immune cells, and therefore, present as potential biomarkers, reflecting the tumor microenvironment. A panel of circulating C-C motif chemokine ligand (CCL) and C-X-C motif chemokine ligand (CXCL) chemokines were examined in the serum of 40 high-grade patients with ovarian cancer prior to primary surgery. The level of immune infiltration in tumors was also analyzed. The preoperative levels of chemokines differ between patients. Elevated levels of circulating CXCL4 + CCL20 + CXCL1 combination can discriminate patients with shorter recurrence-free survival and overall survival. The presence of tumor-infiltrating T lymphocytes was detected in half of the patients. The mRNA expression analysis suggests the presence of antitumoral and immunosuppressive elements in the tumor microenvironment. The combination of circulating CXCL9 + CXCL10 can distinguish immune-infiltrated tumors that will lead to shorter recurrence-free survival. The results suggest that preoperative profiling of circulating chemokines in patients with ovarian cancer may provide valuable information regarding tumor recurrence and immune infiltration. The findings demonstrate that combinations have better prognostic utility than single chemokines, and may serve as patient stratification tools.
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