Shared cancer neoantigens: Making private matters public

Abstract

In this issue of JEM, Chheda et al. (https://doi.org/10.1084/jem.20171046) report that a conserved hotspot mutation associated with an aggressive form of brain cancer generates an immunogenic T cell epitope restricted by a common HLA subtype, thereby creating a "public" neoantigen.

Insight from Christopher A. Klebanoff and Jedd D. Wolchok

The mechanistic basis for the creation of a public neoantigen shared across patients and presented by a prevalent HLA molecule. (A) The majority of diffuse midline gliomas harbor a hotspot mutation resulting in substitution of a methionine for a lysine residue at position 27 of histone variant H3.3 (H3.3K27M). (B) A 10–amino acid peptide harboring this K to M substitution in the second position generates a heteroclitic epitope with a superior binding affinity to the MHC class I molecule HLA-A*02:01. This in turns permits efficient T cell recognition. (C) Table comparing the attributes of patient-specific private neoantigens and shared public neoantigens.