The Human Immunopeptidome Project: A Roadmap to Predict and Treat Immune Diseases*

Immunopeptidomics is a rapidly evolving field that is catalyzed by neoantigen discovery and cancer immunotherapy. Emulating the path of other omic disciplines, Vizcaíno et al. proposes that technological advances in the mass spectrometry field will lead to large immunopeptidomic cohort studies, and ultimately, the immunopeptidome-wide association study (IWAS) paradigm, which will provide profound insights into disease susceptibility and resistance. Graphical Abstract Highlights Immunopeptidomics bears the potential to link diseases to antigen representation. We suggest to achieve this by analyzing the immunopeptidomes of cohorts of patients. Current mass spectrometry-based techniques to analyze immunopeptidomes are described. We term the proposed approach “Immunopeptidome-wide association studies” (IWAS). The science that investigates the ensembles of all peptides associated to human leukocyte antigen (HLA) molecules is termed “immunopeptidomics” and is typically driven by mass spectrometry (MS) technologies. Recent advances in MS technologies, neoantigen discovery and cancer immunotherapy have catalyzed the launch of the Human Immunopeptidome Project (HIPP) with the goal of providing a complete map of the human immunopeptidome and making the technology so robust that it will be available in every clinic. Here, we provide a long-term perspective of the field and we use this framework to explore how we think the completion of the HIPP will truly impact the society in the future. In this context, we introduce the concept of immunopeptidome-wide association studies (IWAS). We highlight the importance of large cohort studies for the future and how applying quantitative immunopeptidomics at population scale may provide a new look at individual predisposition to common immune diseases as well as responsiveness to vaccines and immunotherapies. Through this vision, we aim to provide a fresh view of the field to stimulate new discussions within the community, and present what we see as the key challenges for the future for unlocking the full potential of immunopeptidomics in this era of precision medicine.

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