HLA-DQB1*03:01

Additionally, some patients had more than one and in a few patients had the whole haplotype of BP related HLA. Not only can such enriched presence be considered a role in risk stratification to initiate or continue immunotherapy, but it may shed a light to existing disease genotypes that can become unmasked to phenotypic clinically presenting BP due to immunotherapy rather than just a random AE.

Lastly, HLA-DPB1*05:01:01 was identified as a potential risk HLA allele for development of hepatocellular carcinoma (HCC) in PBC patients. In conclusion, we have extended the current knowledge of HLA allele associations to 3-field resolution and identified novel HLA allele associations with predisposition risk, staging, symptomatic state, and AIH and HCC events for Japanese PBC patients.

Our data shed light on the immunogenetic risk associated with HBV-related HCC. The effect of HLA-DQB1*03:01 could be partly explained by its low binding affinity with HBV nucleocapsid antigen, and/or its effect on viral load control and sPD-1, but not by its control on other inflammation markers (chemokines and cytokines) and viral population diversity. The association between HLA-DQB1 heterozygosity and HCC risk could be independent of the HLA-DQB1*03:01 effect, which indicates underlying mechanisms related to increased immunosurveillance in clearing potential viral antigens or neoantigens.

Our data shed light on the immunogenetic risk associated with HBV-related HCC. 1033

The patient carries the BP-predisposing HLA-DQB1*03:01 allele. In conclusion, anti-PD-1 rechallenge may be considered in metastatic melanoma, even if restarting anti-PD-1 has previously caused the flare-up of BP symptoms.

However, their impact on treatment response is limited, and germline HLA genotypes was not independently associated with survival outcomes. Further prospective studies are needed to confirm the relationship between germline HLA genotypes and clinical outcomes in patients with chemoresistant advanced UC treated with pembrolizumab.

Homozygosity at one or more HLA-I loci can be a useful biomarker to predict irAE among NSCLC patients treated with anti-PD1/PD-L1 in the first- or second-line setting. This is more important among patients who developed pneumonitis or Grade 3 toxicities. However, the occurrence of any irAE is correlated with favourable clinical outcome.