Multiple classes of antigen contribute to the antigenic landscape of mesothelioma.

Abstract

Mesothelioma is an incurable, asbestos-exposure related cancer that typically affects the lining or pleura of the lungs. Symptoms typically develop many decades after initial exposure to asbestos, leaving an enduring legacy of disease. Current disease burden is peaking worldwide and thus there is a massive unmet clinical need for curative therapies. Recently, immune checkpoint blockade-based therapy has been adopted as a first-line of treatment for mesothelioma. Vaccine-induced augmentation of immune responses unleashed during checkpoint blockade may provide further clinical benefit in mesothelioma. In this study we explore the human leukocyte antigen class I landscape (or immunopeptidome) of mesothelioma in patient derived cell line and clinical material (pleural effusion samples). We identify a range of peptide antigens derived from targets including cancer testis antigens, endogenous retroviruses as well as novel post-translational modification of peptides. This information will facilitate the characterization of the immune response to these antigens to determine which class of antigen is most immunogenic and has the potential to be tested in future vaccine studies.