Abstract
BACKGROUND: The comprehensive characterization and prognostic relevance of immune activation in endometrial cancer remain largely unknown. RESULTS: We systematically reported a subset of endometrioid-type endometrial cancer characterized by multifaceted immune features such as low tumor purity, high leukocyte percentage, and striking CD8 lymphocytic infiltration with anti-tumor efficacy along with marked upregulation of immunosuppressive gene markers. We also showed that genes whose expression was significantly correlated with better survival were significantly enriched in the immune-related signaling pathways, suggesting that tumor-infiltrating lymphocytes give rise to a favorable prognosis in endometrial cancer. Furthermore, we showed that immune cell recruitment in this subset of tumors is likely due to the transcriptional activation of the STAT1 signaling network. METHODS: We obtained the multi-dimensional genomic data from publicly available databases and correlated them with the four gene expression-based subtypes we recently identified in endometrial cancer. Upstream regulator analysis was used to identify the most significantly enriched transcription regulators and Ingenuity pathway analysis was applied to determine enrichment of signaling pathways in survival-associated genes. Gene set enrichment analysis was performed on the 200-gene T-cell tumor infiltration gene signature comparing Cluster IV with the other three clusters combined. All statistical tests were two-sided, and a P value of less than 0.05 is considered significant across all analyses performed. CONCLUSION: This study helps to identify patients with immune activation who are likely to benefit from emerging immune checkpoint inhibitors.