The proposed promiscuity value of an HLA can vary significantly depending on the source data used

ABSTRACT Immune checkpoint blockade, a form of immunotherapy, mobilizes a patient’s own immune system against cancer cells by releasing some of the natural brakes on T cells. Although our understanding of this process is evolving, it is thought that a patient response to immunotherapy requires tumor presentation of neoantigens to T cells and patients whose tumors present a wider array of neoantigens are more likely to derive benefit from immune checkpoint blockade 1–4 . Manczinger et al. 5 recently reported findings that would appear contrarian to this notion in that they suggested patients with HLA alleles which bind more diverse peptides (higher promiscuity) are less likely to respond to immunotherapy. To estimate HLA promiscuity they looked at the HLA-peptide binding repertoires for class I alleles contained in the IEDB 6 , and obtained consistent results when performing robustness checks and subsequent analyses. Here we show that the proposed HLA promiscuity values can vary significantly across source data types and individual experiments.