Annotation Detail

Information

Associated Genes: HLA-DRA
Associated Variants: HLA-DRA EXPRESSION
HLA-DRA EXPRESSION
Associated Disease: skin melanoma
Source Database: CIViC Evidence
Description: Melanoma patients treated with Anti-PD1 or anti-PD-L1(nivolumab, pembrolizumab, MPDL3280A) therapy were analyzed for expression of HLA-DRA (the primary antigen-presenting molecule of the MHC-II pathway). In a discovery cohort, 30 patients underwent IHC for HLA-DRA. 11/14 (79%) patients with positive HLA-DR staining, had complete (n=3) or partial (n=8) response. 6/16 (38%) HLA-DR non-expressing melanomas responded to therapy (overall response rate 79 versus 38%, Fisher’s exact test P=0.033). This finding was confirmed in a second independent data set of 23 melanoma patients with 6/8 (75%) of HLA-DR(+) tumours in comparison to 4/15 (27%) HLA-DR(−) responding (Fisher’s exact test P=0.025). Preclinical models confirmed the result.
Variant Origin: N/A
Variant Origin: N/A
Evidence URL: https://civic.genome.wustl.edu/links/evidence_items/985
Gene URL: https://civic.genome.wustl.edu/links/genes/2622
Variant URL: https://civic.genome.wustl.edu/links/variants/423
Rating: 3
Evidence Type: Predictive
Disease: Skin Melanoma
Evidence Direction: Supports
Drug: Pembrolizumab,Atezolizumab,Nivolumab
Evidence Level: B
Clinical Significance: Sensitivity/Response
Pubmed: 26822383

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