Combined analysis of antigen presentation and T cell recognition reveals restricted immune responses in melanoma [Research Briefs]

The quest for tumor-associated-antigens (TAAs) and neo-antigens is a major focus of cancer immunotherapy. Here we combine a neo-antigen prediction-pipeline and human-leukocyte-antigen (HLA)-peptidomics to identify TAAs and neo-antigens in 16 tumors derived from seven melanoma patients, and characterize their interactions with their TILs. Our investigation of the antigenic and T-cell landscapes encompassing the TAA and neo-antigen signatures, their immune reactivity, and their corresponding T-cell identities provides the first comprehensive analysis of cancer cell T-cell co-signatures, allowing us to discover remarkable antigenic and TIL similarities between metastases from the same patient. Furthermore, we reveal that two neo-antigen-specific clonotypes killed 90% of autologous melanoma cells, both in vitro and in vivo, showing that a limited set of neo-antigen-specific T-cells may play a central role in melanoma tumor rejection. Our findings indicate that combining HLA-peptidomics with neo-antigen predictions allows robust identification of targetable neo-antigens, which could successfully guide personalized cancer-immunotherapies.

https://ift.tt/2x654JM