American Association for Cancer Research
21598290cd200672-sup-243330_2_supp_6676976_q1tb8l.pdf (27.49 kB)

Supplementary Data Table S2 from Somatic HLA Class I Loss Is a Widespread Mechanism of Immune Evasion Which Refines the Use of Tumor Mutational Burden as a Biomarker of Checkpoint Inhibitor Response

Download (27.49 kB)
journal contribution
posted on 2023-04-03, 22:25 authored by Meagan Montesion, Karthikeyan Murugesan, Dexter X. Jin, Radwa Sharaf, Nora Sanchez, Ameet Guria, Max Minker, Gerald Li, Virginia Fisher, Ethan S. Sokol, Dean C. Pavlick, Jay A. Moore, Alan Braly, Gaurav Singal, David Fabrizio, Leah A. Comment, Naiyer A. Rizvi, Brian M. Alexander, Garrett M. Frampton, Priti S. Hegde, Lee A. Albacker

Sample counts by tumor type



Neoantigen presentation arises as a result of tumor-specific mutations and is a critical component of immune surveillance that can be abrogated by somatic LOH of the human leukocyte antigen class I (HLA-I) locus. To understand the role of HLA-I LOH in oncogenesis and treatment, we utilized a pan-cancer genomic dataset of 83,644 patient samples, a small subset of which had treatment outcomes with immune checkpoint inhibitors (ICI). HLA-I LOH was common (17%) and unexpectedly had a nonlinear relationship with tumor mutational burden (TMB). HLA-I LOH was frequent at intermediate TMB, yet prevalence decreased above 30 mutations/megabase, suggesting highly mutated tumors require alternate immune evasion mechanisms. In ICI-treated patients with nonsquamous non–small cell lung cancer, HLA-I LOH was a significant negative predictor of overall survival. Survival prediction improved when combined with TMB, suggesting TMB with HLA-I LOH may better identify patients likely to benefit from ICIs. This work shows the pan-cancer landscape of HLA-I LOH, revealing an unexpected “Goldilocks” relationship between HLA-I LOH and TMB, and demonstrates HLA-I LOH as a significant negative predictor of outcomes after ICI treatment. These data informed a combined predictor of outcomes after ICI and have implications for tumor vaccine development.This article is highlighted in the In This Issue feature, p. 211

Usage metrics

    Cancer Discovery



    Ref. manager