Revisiting the Neoantigen approach to cancer immunotherapy

Immunotherapy has sparked new hope for oncology in recent years, due to its remarkable ability to induce long-term tumor regression of metastatic cancer. Accumulating evidence suggest that tumor regression observed with immunotherapy are driven by targeted elimination of antigen-bearing tumor cells that are explicitly recognized by T-lymphocytes.

Our systematic analysis of melanoma tumors for HLA-presented peptides using HLA peptidomics has allowed us to identify cancer/melanoma antigens, neo-antigens, intracellular microbial antigens and aberrant peptides. Our studies reveal that the landscape of melanoma-presented HLA-peptides is highly complex. We will discuss relevant mechanisms, effects on immune recognition and therapeutic implications.