The Neoantigen And Immune Landscape Of Low And High Grade Serous Ovarian Cancers.

Abstract Background: Within serous ovarian cancer (SOC), high-grade serous carcinoma (HGSC) demonstrates a worse prognosis compared to low-grade serous carcinoma (LGSC). Molecular analysis of SOC has revealed a distinct pattern of mutations found between the two pathologic subtypes, with TP53 as the main driver for HGSC. We analyzed the neoantigen and immune landscape of different SOC subtypes according to pathological grades and mutation status. Methods: The analysis was done using the SOC cohort of The Cancer Genome Atlas (TCGA). The neoantigen prediction was done through the CloudNeo pipeline. CIBERSORT was applied to derive the tumor-infiltrating immune cells. Patients were grouped by their pathological grades (high vs. low) and the molecular features (type 1 vs. 2). For further subgroup analysis, high-grade samples were stratified by their TP53 mutation status. Results: Among 585 SOC patients, a subset of 254 patients with available mutation counts and predicted neoantigen counts were included. There was no significant difference in neoantigen count between low and high grades (median 50.50 vs. 62.50, p=0.84). However, there was a trend for differential numbers in the neoantigen count between type 1 and type 2 (median 29 vs. 66.50, p=0.07). No notable differences were detected in immune landscapes of low vs. high grade and type 1 vs. type 2. Conclusions: Our study is the first to describe the neoantigen and immune landscape of SOC. There were no significant differences in the immune landscape between the subtypes. It seems that molecular subtyping is more related to neoantigen differences than histologic subtyping. It is likely that the neoantigen differences are not defined by the histologic grade but rather by molecular trait. The immunologic characteristics of EMT low and high SOCNumber of ptientsNeoantigen countp-valueMutation countp-valueCytolytic scorep-valuePD-L1 expressionp-valueLow grade1250.500.84700.8757.120.4812.340.28High grade8062.5085.571.0919.66Type 117290.07114.60.98125.10.7824.940.77Type 222066.50115.3119.526.3High grade(TP53 wild type)744.000.06620.08163.20.0629.770.5High grade(TP53 mutated)7364.0086110.126.47TCGA cohort provided the data of low(GB, G1, G2) and high(G3, G4) grade SOCsType 1: Defined as mutations in KRAS, BRAF, PTEN, PIK3CA, CTNNB1 and ARID1A irrespective of histologic gradeType 2: Defined as mutation in TP53 irrespective of histologic gradeThe samples that had intersecting mutations were excluded in type 1 and type 2.The cytolytic activity score was defined as a geometric mean of mRNA expression of perforin and granzyme. Citation Format: Won Kyung Hur, Jin Young Hwang, Leeseul Kim, Myungwoo Nam, William H. Bae, Yoonhee Choi, Yeun Ho Lee, William Cheng, Heayoon S. Cho, Emma Yu, Chan Mi Jung, Eugene Kim, Christmann Low, Victor Wang, Jeff Chuang, Young Kwang Chae. The neoantigen and immune landscape of low and high grade 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 453.