Cancer immunotherapy has emerged as a transformative approach in oncology. This therapeutic approach includes various strategies such as immune checkpoint inhibitors, adoptive cell transfer and cancer vaccines. Human leukocyte antigen (HLA) molecules are essential for effective immune responses since they display tumour derived peptides on the cell surface leading to their recognition and killing by T cells. One innovative strategy is to study the soluble HLA (sHLA) peptide repertoire using relatively non-invasive plasma. The level of plasma HLA is known to change in cancers, a disproportionate fraction of peptides bound to plasma HLA originate from tumour tissue. In this study, we leverage recent advances in the throughput and sensitivity of both liquid chromatography (LC) and mass spectrometry (MS) to create a highly sensitive workflow for plasma immunopeptidomics. This study involves investigation of plasma immunopeptidome and proteome acquired longitudinally from patients across different cancers including leukaemia, triple negative breast cancer and melanoma with different treatment regimens.
For example, in a preliminary study of AML patients, sHLA was isolated from plasma was compared with that bound to mHLA in bone marrow (BM) and peripheral blood cells. Despite relatively limited availability of clinical material, a total of 31,000 HLA class I -bound peptides were identified from three patients with ~16,000 unique peptides identified from only 3mL of plasma. There was an overlap of ~25% between the immunopeptidome of the BM, PBMCs and plasma from the same individual including peptides derived from cancer testis and other tumour associated antigens.
In conclusion, I present a robust clinical proteomics and immunopeptidomics platform that provides insights into the dynamic nature of tumour antigen presentation. The approach of combining immunopeptidomics with proteomics and transcriptomics aides both identification of biomarkers of disease and clinical response, but also T cell-based immunotherapy.