Research

Deciphering the Immunopeptidomic Landscape in Melanoma

Immunotherapy such as immune checkpoint inhibitors has revolutionized cancer treatment, showing great success in treating patients with advanced or refractory disease and in preventing tumor recurrence following surgery. This form of cancer therapy relies greatly on the ability of cytotoxic T cells to specifically recognize diseased cells within the tumor microenvironment and mark them for elimination. The key to this vital recognition is the unique set of tumor-associated antigens or antigens derived from mutant proteins (neoantigens) adorning cancerous cells, which together constitute the cancer immunopeptidome.

Identification of Recurrently Presented Neoantigens

A major hallmark of cancer is somatic mutations. These may lead to the generation of clinically relevant neoantigens. However, most neoantigens identified to date arise from private somatic mutations, limiting their effectiveness to the individual patient and possibly only to the sub-clonal part of the tumor, increasing the risk of treatment resistance. Thus, to develop ‘off-the-shelf’ precision immunotherapies that cater to a large group of patients, there is a need to identify hotspot neoantigens.

Identifying Novel Antigen Sources to Stimulate Tumor Immune Response

To decipher the process of tumor immune rejection, it is essential to identify the cancer-specific immunopeptidome determined under various conditions. Despite intense investigations, there are still key gaps in our knowledge as to which aberrant peptides are presented and in which contexts. Our goal is to decipher the different layers of the complex cancer peptidome and link it to knowledge regarding the main signaling pathways driving cancer, as the cancer immunopeptidome reflects these tumorigenic cellular pathways. We will thus expand our understanding of the effects of the different hallmarks of cancer on aberrant peptide presentation as a means to comprehensively identify and characterize the antigenic hallmarks of cancer

Identifying Biomarkers for Immunotherapy

Clonal neo-antigen burden has been associated with improved response to immunotherapy, however, the functional basis for this remains unclear. The search for reliable biomarkers, including clonal neoantigen burden, is ongoing and is crucial for understanding and predicting patient response to immunotherapy. Since most studies in this field are correlations between clinical results and these various biomarkers, our goal is to set up mouse models in which we can tease apart the relevant biomarkers.