Máté Manczinger: Neoantigen repertoire in the context of HLA class I shapes antitumor immunity

Full title: Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity.

The HLA-I molecules help our immune system fight off diseases and cancer by recognizing specific peptides. Some HLA-I variants can bind a wide variety of peptides, which could be helpful against viruses but its implications on cancer immune response are unknown. Our study found that cancer patients with HLA-I variants that bind many different peptides have worse survival when treated with immune checkpoint blockade immunotherapy. This seems to be because their immune system has trouble differentiating between cancer proteins and normal body proteins, making it more likely to ignore cancer cells. In essence, the ability of HLA-I variants to bind many peptides may compromise the fight against cancer while possibly offering protection against viruses.

Máté Manczinger graduated with a medical degree from the University of Szeged in 2010 and he pursued further studies in dermatology and immunology. By 2016, he had completed Ph.D. and a dermatologist specialization. He has become a principal Investigator at the Biological Research Centre, Szeged, Hungary in 2022. Under his direction, the concept of HLA promiscuity has been thoroughly examined, resulting in significant publications in PLoS Biology and Nature Cancer. His latest work, in collaboration with Thomas Vogl and Sasha Zhernakova, investigates the relationship between HLA promiscuity and antibody diversity.