Abstract B070: Neoepitope and mutation load as a biomarker in a broad cohort of cancer patients treated with immunotherapy

Abstract

Abstract Various different treatments of immunotherapy have in recent years made their mark in mainstream oncology, but it is still uncertain which patients will benefit and why. To determine this, different biomarkers have been investigated including tumor specific peptides originating from somatic mutations and recognized by T-cells, neoepitopes. Recent studies show that clinical benefit of immunotherapy correlate with both high mutational burden and high neoantigen load in defined patient groups, melanoma and lung cancer, underlining the possibility to use these measurements as biomarkers, and driving the hypothesis that neoantigen-responsive T-cells are the main drivers to cancer-cell elimination. We propose to investigate if a high mutational load and a high amount of neoepitopes are correlated with a general respond to immunotherapy across different cancer types and immunotherapy treatments. To examine this correlation, we studied 19 patients who have been treated with different kinds of immunotherapy. The data consist of Whole Exome Sequencing (WXS) data from blood and tumor, as well as tumor mRNA sequencing from all patients. Neoepitope load was predicted using Mutant peptide extractor and informer (MuPeXI) to find possible neoepitopes and score the neopeptides by their potential immunogenicity. The analysis of the sequencing data from the 19 patients revealed that even though these patients have cancers of varying origin and treated with different immunotherapies, a significant correlation was observed between a high number of neoepitopes as well as high mutational load with an increased possibility of a clinical benefit to immunotherapy. These findings showed that overall a clinical benefit is correlated with increased mutational load and neoepitopes independent of the cancer type and treatment which if used as a biomarker can possibly stratify patients determining who is likely to respond to cancer immunotherapy. Furthermore, we examined the tumor mRNA for T-cell recpetor sequences, and interestingly patients with high level of predeicted neoepitopes show enhanced oligoclonality of TCRs at the tumor site. Citation Format: Anne-Mette Bjerregaard, Vinicius Araujo Barbosa de Lima, Annie Borch, Olga Araujo Barbosa de Oestrup, Ulrik Lassen, Sine Reker Hadrup. Neoepitope and mutation load as a biomarker in a broad cohort of cancer patients treated with immunotherapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B070.