Vol.:(0123456789) 1 3 Mammalian Genome (2018) 29:757–769 https://doi.org/10.1007/s00335-018-9763-6 The role of proteomics in the age of immunotherapies Sarah A. Hayes 1,2  · Stephen Clarke 1,2,3  · Nick Pavlakis 1,2,3  · Viive M. Howell 1,2 Received: 5 April 2018 / Accepted: 20 July 2018 / Published online: 25 July 2018 © Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract The antigenic landscape of the adaptive immune response is determined by the peptides presented by immune cells. In recent years, a number of immune-based cancer therapies have been shown to induce remarkable clinical responses through the activation of the patient’s immune system. As a result, there is a need to identify immune biomarkers capable of predicting clinical response. Recent advances in proteomics have led to considerable developments in the more comprehensive profling of the immune response. “Immunoproteomics” utilises a rapidly increasing collection of technologies in order to identify and quantify antigenic peptides or proteins. This includes gel-based, array-based, mass spectrometry (MS), DNA-based, or computer-based (in silico) approaches. Immunoproteomics is yielding an understanding of disease and disease progression, vaccine candidates, and biomarkers to a depth not before understood. This review gives an overview of the emerging role of proteomics in improving personalisation of immunotherapy treatment. Introduction In recent years, it has become clear that immunotherapy, previously thought to be useful in only a few select malig- nancies, has signifcant clinical activity in a variety of can- cers including melanoma, lung, bladder, head and neck, cervical, and most recently, solid cancers with mismatch repair-defciency (reviewed in Dholaria et al. 2016; Sharma and Allison 2015; Syn et al. 2017). Advances in the area of immunotherapy for treatment of these cancers is based on our increased understanding of tumourigenesis and cancer progression, which involve accumulating mutations that result in a diverse set of antigens that the immune system can use to distinguish cancer cells from normal cells. This increased understanding of the immune system plus the development of immune modulation techniques have led to a new era in cancer therapy, which harnesses our own immune system to treat cancer. Under normal circumstances, to ensure that the immune system does not harm the host when reacting to a foreign antigen, humans have evolved immune checkpoint pro- teins (ICPs) to quickly stop an immune response. However, when cancer develops in a patient, multiple mechanisms of immune suppression activate to prevent efective anti- tumour immunity (Li et al. 2018). The ICPs are cell sur- face receptors expressed by immune cells that regulate the activation and efector functions of T lymphocytes, which are modulated by a set of co-stimulatory and co-inhibitory molecules (reviewed in detail in Haanen and Robert 2015; Pardoll 2012; Rowshanravan et al. 2018). The best characterised ICPs—and the most actively exploited in the context of cancer immunotherapy—are cytotoxic T-lymphocyte protein 4 (CTLA-4) and the pro- grammed cell death protein 1 pathway (PD-1 receptor/ PD-L1 and PD-L2 ligands). The most well-prescribed can- cer immunotherapies target those co-inhibitory T-cell check- point receptors using ipilimumab (CTLA-4) and nivolumab/ pembrolizumab (PD-1) to reverse immune “exhaustion” and improve tumour responses. Other cancer immunotherapies have been approved for use in recent years, including pre- ventive and therapeutic cancer vaccines, a bi-specifc T-cell engager (Topp et al. 2011), and an oncolytic virus (Andt- backa et al. 2015). Of these, immune checkpoint antago- nists that target the PD-1 pathway have generated the most * Sarah A. Hayes sarah.hayes@sydney.edu.au 1 Bill Walsh Translational Cancer Research Laboratory, Hormones and Cancer, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, Sydney, Australia 2 Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia 3 Department of Medical Oncology, Royal North Shore Hospital, St Leonards, Sydney, Australia