Abstract B187: Origins of neoantigens for the major histocompatibility complex class I pathway

Neoantigens are antigens generated by somatic mutations that can be recognized by the host immune system, firstl described as differentiating or tumor antigens back in 80s and 90s in research related to mice melanoma and breast cancers carried out by Houghton’s and Cheever’s teams, respectively. Now, during the era of potent immunotherapies, cancer vaccines and checkpoint inhibitors (CTLA-4, PD-1), neoantigens again attract much of scientists’ attention. With the use of cutting-edge technologies like next-generation sequencing, mass spectrometry, and predictive algorithms, more is known about antigen presentation and the links between occurrence of somatic mutations in cancer cells and antigen recognition by CD8+T-cells. Interestingly, discoveries of alternative sources of antigenic peptides (e.g., DRIPs and PTPs) challenged the notion about full-length proteins being the main supplier of material for MHC class I pathway and shifted focus of search for new sources to ribosomal scanning during pioneer round of translation. Despite the fact that pathways involved in processing and presentation of peptides have been thoroughly studied, there is still more to be learned about the sources of peptide material for the endogenous and exogenous MHC class I pathways. Based on works related to Epstein-Bar virus, it has been shown that MHC class I immune surveillance is directly correlated with the mechanism that regulates protein synthesis. Together with other results, it highlights the importance of pre-mRNA and mRNA processing in providing antigenic peptides for MHC class I surveillance. Here we revise some significant research related to the production of alternative antigenic peptides, their importance in cancer research, immunosurveillance and generation of tolerance. The lack of animal models to study the origin of alternative antigenic peptides hinders research in the field of neoantigens. I will describe results of the presentation of intron-derived antigenic peptides in mice model developed by our team. Citation Format: Ewa Maria Sroka, Rodrigo Prado Martins, Chrysoula Daskalogianni, Sebastien Apcher, Robin Fahraeus. Origins of neoantigens for the major histocompatibility complex class I pathway [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 B187.