Abstract 30P
Background
Human leukocyte antigen (HLA) is a gene complex encoding major histocompatibility complex (MHC) proteins. HLA-A, HLA-B, and HLA-C are three main HLA class I genes that present peptides to cell surface, leading immune system to destroy the cells. Loss of heterozygosity (LOH) at HLA locus reduces the capacity of neoantigen presentation, thereby aiding immune evasion of tumors.
Methods
We developed an HLA typing method based on a Bayesian classification algorithm called Polysolver, which deciphers HLA type from 539-gene panel genomic data by next-generation sequencing. The method was validated on samples with the standard PCR-SBT (sequencing-based typing) results. HLA-LOH was determined by comparing HLA typing results between paired tumor and white blood cell samples. We performed the HLA typing and HLA-LOH analysis on 1342 real-world clinical samples across 17 cancer types, mostly lung cancer (LC), liver cancer (HCC), and colorectal cancer (CRC).
Results
Within all 1342 samples, 279 (20.8%) carried at least one homozygous HLA gene, which indicates that most individuals with no homozygous HLA gene may benefit better from targeted therapies than others, according to previous studies. LOH results (on HLA-A, HLA-B, and HLA-C) were available in 524 FFPE samples with at least 50% tumor ratio (H&E stain). Within the 524 samples, 118 (22.5%) carried at least one LOH gene, in which LC had the highest LOH ratio (25.8%, 41/159) among different cancer types. Among all samples with HLA-LOH, more than 50% of them had all three genes with LOH, suggested that the three genes tended to be lost at the same time. Patients with LOH gene had significantly higher TMB than patients without LOH gene (mean TMB: 6.57 vs. 5.19, p = 0.0003). LOH ratio is significantly higher in elder patients (28.0%, 63/225, age above 60) than younger patients (13.18%, 11/80, age below 40), suggested that immunotherapy may be less responded in elder patients. No significant correlation was found between LOH ratio and PD-L1 expression.
Conclusions
We established an accurate HLA typing method and investigated the prevalence of HLA typing and HLA-LOH in Chinese cancer patients, which may provide references and insights for further immunotherapy research.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.