Abstract 1972: Clinical implications of HLA expression and immunopeptidome-presented tumor antigens in ovarian carcinoma
Authors: Tegeler Christian M. , Heitmann Jonas S. , Salih Helmut R. , Walz Juliane S. , Nelde Annika 
Published: June 2022

Ovarian carcinoma (OvCa) is the seventh most common malignancy in women and the eighth leading cause of cancer-related deaths worldwide. In a previous study, we characterized the antigenic landscape of ovarian carcinoma by mass spectrometry-based immunopeptidomics and identified novel OvCa-associated tumor antigens, including Mucin-16 (MUC-16) and Mesothelin (MSLN) with the aim to develop novel T cell-based immunotherapies (Schuster et al. PNAS 2017). Here, we analyzed the immunopeptidomics data of this OvCa cohort in relation to clinical patient characteristics and disease outcome. Analysis included 43 OvCa patients with respective immunopeptidomics and RNA sequencing data, comprising immunopeptidome diversity, tumor antigen presentation and expression (MUC16, MSLN) as well as HLA mRNA expression.Analyzing HLA class I-restricted tumor antigen presentation in relation to clinical data, we could show that nodal-positive patients presented more frequently HLA-restricted peptides derived from the tumor antigen MUC16 (p = 0.0087) and showed significantly increased numbers of unique MUC16-derived HLA-presented peptides within the total immunopeptidome (p = 0.042) compared to nodal-negative patients. No significant difference in HLA class I immunopeptidome diversity, overall tumor antigen presentation, and expression was observed for histological subtypes, grading, or the prevalence of distant metastases. For HLA class II-restricted tumor antigen presentation and HLA expression in relation to clinical data, we observed a more diverse HLA class II immunopeptidome in terms of different HLA class II-presented peptides (p = 0.011) for patients with high tumor grading (G3) compared to low/intermediate (G1/G2) grading. In line, the tumors of these patients also presented an increased number of different MSLN-derived HLA class II-restricted peptides (p = 0.021). No significant difference in HLA class II immunopeptidome diversity, tumor antigen presentation and expression was seen for the prevalence of distant metastasis, histological subtypes, or nodal positivity.Of note, patients presenting MSLN-derived peptides in their immunopeptidome showed a significantly prolonged recurrence-free survival (RFS, p = 0.011). In addition, patients exhibiting a high expression of HLA-DR showed a significantly increased RFS (p = 0.018 for HLA-DRA, p = 0.0031 for HLA-DRB).In conclusion, this work provides first insights on the relation of immunopeptidomic characteristics, comprising HLA expression and tumor antigen presentation, with clinical characteristics and disease outcome of OvCa patients. The observed correlation of HLA-DR expression and HLA class II tumor antigen presentation with prolonged RFS indicates a central role of CD4+ T cell responses for anti-tumor immune surveillance in ovarian cancer.

Citation Format: Christian M. Tegeler, Jonas S. Heitmann, Helmut R. Salih, Juliane S. Walz, Annika Nelde. Clinical implications of HLA expression and immunopeptidome-presented tumor antigens in ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1972.