The prevalence of HLA LOH across 10 cancer types in Chinese patients.

Abstract

3124 Background: Recognition of tumor neoantigen is the key to generating immune response. The expression and integrity of human leukocyte antigen (HLA) are the prerequisites for neoantigen presentation, and loss of heterozygosity in HLA (HLA LOH) may facilitate immune evasion. However, the incidence of HLA LOH in Chinese cancer patients is unknown. Methods: In this study, 45 samples sequenced with both 1021-gene panel and whole-exome sequencing(WES) were used to evaluate the consistency of HLA LOH in the two testing strategies. The prevalence of HLA LOH analysis was performed in 1546 advanced patients across 10 diverse cancer types and 114 early-stage lung cancer patients who had undergone tumor profiling using 1021-gene panel. Exon 2, exon 3 and bilateral introns of HLA-A/B/C genes were well covered in 1021-gene panel. HLA LOH were analysis using LOHHLA algorithm (McGranahan, et al. 2017). Results: In the HLA LOH analysis of 45 samples, the consistency of 1021-gene panel and WES was 95.6% (43/45). Among the 1660 samples, 1.3% (21) were detected as HLA homozygous at all of the three site. HLA LOH was found in 45.1%(697/1546) of all the advanced patients, range from 24.1% to 59.7%. In colorectal cancer, the HLA LOH ratio of MSS samples was significantly higher than that of MSI-H samples (46.2%, 61/132 vs 16.7%, 3/18 p =0.0214). For NSCLC, the proportion of HLALOH in early-stage (I-IIIa) lung adenocarcinoma and lung squamous cell carcinoma was 25.7% (18/70) and 65.9% (29/44), respectively, consistent with the report. However, advanced (IIIa-IV) lung adenocarcinoma and lung squamous cell carcinoma were 49.4%(168/340) and 58.7%(179/305), respectively. The reason for the difference between early-stage lung adenocarcinoma and advanced lung adenocarcinoma needs further study. In 43.8% of cases (326/744), LOH occurred simultaneously in HLA-A, B and C,suggesting that the Class I locus was often lost together. Conclusions: We can use multi-gene panel for HLA LOH analysis, provided that the relevant regions are well captured. The prevalenceof HLA LOHpresent differences among cancer types.Understanding these distributions may provide more information for immunotherapy research. [Table: see text]