Assessment of Human Leukocyte Antigen-Based Neoantigen Presentation To Determine Pan-Cancer Response to Immunotherapy

Authors

Jiefei Han
Yiting Dong
Xiuli Zhu
Alexandre Reuben
Jianjun Zhang
Jiachen Xu
Hua Bai
Jianchun Duan
Rui Wan
Jie Zhao
Jing Bai
Xuefeng Xia
Xin Yi
Chao Cheng
Jie Wang
Zhijie Wang

Publication Date

2-8-2024

Journal

Nature Communications

Abstract

Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment. Analysis of the tumor microenvironment indicated that the antigen presentation pathway was enriched in patients with a high HAPS. Finally, we built a neural network incorporating factors associated with neoantigen production, presentation, and recognition, which exhibited potential for differentiating cancer patients likely to benefit from ICIs. Our findings highlight the clinical utility of evaluating HLA-I tumor antigen presentation capacity and describe how ICI response may depend on HLA-mediated immunity.

Keywords

Humans, Neoplasms, Histocompatibility Antigens Class I, Antigens, Neoplasm, Histocompatibility Antigens Class II, HLA Antigens, Immunotherapy, Tumor Microenvironment

Comments

Supplementary Material

Data Availability Statement

PMID: 38331912

DOI

10.1038/s41467-024-45361-5

PMID

38331912

PMCID

PMC10853168

PubMedCentral® Posted Date

February 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes