Human leukocyte antigen (HLA) class I encompasses peptide-binding proteins that regulate T-cell interactions. We examined HLA class I expression in prostate cancers (PC), exploring associations with clinical outcomes, molecular features, and tumor immune microenvironment.
We analyzed 8040 PC samples from the Caris Life Sciences database, stratifying them into HLA-high (upper quartile) and -low (lower quartile) groups. Genomic and transcriptomic alterations were compared. Immune cell fractions were inferred using quanTIseq, and overall survival (OS) data was obtained from insurance claims. Differences were computed with Cox proportional hazards.
Among 66 cancer types, PC ranked 3rd-, 11th-, and 19th-lowest for HLA-A, -B, and -C expression, respectively. In PC, genes tied to androgen receptor (AR) signaling, immune checkpoint molecules (CTLA4, PD-L1), and the epithelial-mesenchymal transition were significantly higher in HLA-high tumors. HLA-high status was linked to greater tumor immune activity, marked by higher T cell fractions and enhanced immune hallmarks. HLA-high tumors were less likely to possess alterations in AR, FOXA1, and CDK12, but harbored increased alterations in tumor suppressor gene (RB1, PTEN) alterations. Tumors with high HLA-A and HLA-B had elevated TMB-H/MSI-H/dMMR status. Finally, shorter OS was observed in patients with high HLA-A or HLA-B expression, while longer OS was associated with high HLA-C expression.
In PC, elevated HLA class I levels correlate with immune activity, molecular characteristics, and clinical outcomes. We suggest considering HLA expression as a supplementary marker of immune activity in PC, alongside genetic mutations and transcriptomic markers.
Prostate cancer and prostatic diseases. 2025 Oct 25 [Epub ahead of print]
Pornlada Likasitwatanakul, Carissa Besonen, Alexander K Tsai, Negar Sadeghipour, Andrew Elliott, Ali T Arafa, Rachel Passow, Lisa Chesner, Martin Felices, Philippa R Kennedy, Akash Patnaik, Vivek Narayan, James Hamrick, Laura A Sena, Nicholas A Zorko, Justin H Hwang, Emmanuel S Antonarakis
Department of Medicine, University of Minnesota-Twin Cities, Minneapolis, MN, 55455, USA., School of Medicine, Creighton University, Omaha, NE, 68178, USA., Department of Medical Affairs, Caris Life Sciences, Irving, TX, 85040, USA., Masonic Cancer Center, University of Minnesota-Twin Cities, Minneapolis, MN, 55455, USA., Department of Urology, University of California San Francisco, San Francisco, CA, 94115, USA., Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, 60637, USA., Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, 21231, USA., Department of Medicine, University of Minnesota-Twin Cities, Minneapolis, MN, 55455, USA. ., Department of Medicine, University of Minnesota-Twin Cities, Minneapolis, MN, 55455, USA. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41139148