Abstract 626: The neoantigen and immune landscape of epithelial mesenchymal transition (EMT) low and high score serous ovarian cancers

Abstract

Background: Apart from its role in ovarian cancer progression, epithelial-mesenchymal transition (EMT) can promote chemotherapy resistance. We aimed to analyze how the EMT score would affect the tumor microenvironment in ovarian cancer. Methods: cBioportal was queried to obtain The Cancer Genome Atlas (TCGA) data for the serous ovarian cancer (SOC) cohort (TCGA, 585 patients). The neoantigen prediction data was derived from the CloudNeo pipeline using TCGA mutation calling. EMT scores were calculated by subtracting the average RNA-seq z-scores of three epithelial marker genes from the average RNA-seq z-scores of 13 mesenchymal marker genes as described in the previous study. Patient samples were grouped as either EMT-high (highest 1/3) or EMT-low (lowest 1/3). CIBERSORT was applied to predict the tumor-infiltrating immune cells. Results: Among the 585 SOC patients, only 256 patients had mutation data available for our analysis. The EMT-low group had a significantly higher mutation count (p value=0.0004) and cytolytic score (p value=0.032) than the EMT-high group. In addition, the EMT-low samples were associated with improved overall survival in SOC patients (HR, 0.55; 95% CI, 0.39-0.78; P < 0.001). The median survival of EMT-low was 57.40, and EMT-high was 41.06 months. Neoantigen counts and PD-L1 express level tended to be higher in the EMT-high group although failed to show statistical significance. The immune cell infiltration rates were not different between both groups. Conclusions: Our study is the first to describe the association between the EMT potential, neoantigen counts, and cytolytic scores in SOC. In our analyses, tumors with low EMT potential had a significantly higher neoantigen burden and higher cytolytic scores, suggesting that tumors with low EMT potentials tend to be more immunogenic. Further studies are warranted to explore the utility of EMT scores as biomarkers to predict the treatment response to immunotherapy in SOC. The immunologic characteristics of EMT low and high SOCNumber of patientsNeoantigen countp-valueMutation countp-valueCytolytic scorep-valuePD-L1 expressionp-valueEMT low6088.190.183783.190.0004183.40.032190.0663EMT high5867.7472.7486.3515.52 Citation Format: Won Kyung Hur, Jin Young Hwang, Leeseul Kim, Myungwoo Nam, William H. Bae, Yoonhee Choi, Yeun Ho Lee, Heayoon S. Cho, Emma Yu, Chan Mi Jung, William Cheng, Eugene Kim, Christmann Low, Victor Wang, Jeff Chuang, Young Kwang Chae. The neoantigen and immune landscape of epithelial mesenchymal transition (EMT) low and high score serous ovarian cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 626.

Programmed Death Ligand 1 (PD-L1) Expression and CD8+ Tumor-infiltrating Lymphocyte-based Tumor Immune Microenvironment Classification in Gynecologic Carcinosarcoma: Prognostic Impact and Implications for Therapy

“…Lien et al (44) found a high TIL density in 34% of metaplastic breast carcinoma, a tumor similar to CS both in its association with epithelialmesenchymal transformation (EMT) and extremely low rate of MSI (44,45). A study of ovarian serous carcinoma has suggested that tumors with high EMT scores may have higher numbers of neo-antigens compared to tumors with low EMT scores (46). Whether EMT causes increase in immunogenicity of CS leading to influx of TILs needs to be explored in future studies.…”