Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity

• Published in: Molecular oncology Vol. 16; no. 19; pp. 3452 - 3464
• Main Authors: Classon, Johanna, Zamboni, Margherita, Engblom, Camilla, Alkass, Kanar, Mantovani, Giulia, Pou, Christian, Nkulikiyimfura, Dieudonné, Brodin, Petter, Druid, Henrik, Mold, Jeff, Frisén, Jonas
• Format: Journal Article
• Language: English
• Published: Hoboken John Wiley & Sons, Inc 01-10-2022; John Wiley and Sons Inc; Wiley
• Subjects: Alleles; Antigen presentation; Antigens; Antiviral agents; antiviral protection; Biomarkers; Confidence intervals; Consent; Cytomegalovirus; cytomegalovirus (CMV); Cytomegalovirus infections; Development and progression; Diseases; Epstein-Barr virus; Ethics; Gene expression; Genes; Genomes; Histocompatibility antigen HLA; Histocompatibility antigens; HLA histocompatibility antigens; HLA‐alleles; Influenza; Medical prognosis; Medical research; Medicin och hälsovetenskap; Medicine, Experimental; Metastases; Metastasis; Mutation; Patients; Prognosis; Prostate cancer; Prostatectomy; Relapse; Risk assessment; Surgery; T cell receptors; T cells; Tumors; United States > US
• ISSN: 1574-7891; 1878-0261; 1878-0261
• DOI: 10.1002/1878-0261.13273

Prostate cancer is a heterogeneous disease with a need for new prognostic biomarkers. Human leukocyte antigen (HLA) genes are highly polymorphic genes central to antigen presentation to T‐cells. Two alleles, HLA‐A*02:01 and HLA‐A*24:02, have been associated with prognosis in patients diagnosed with de novo metastatic prostate cancer. We leveraged the next‐generation sequenced cohorts CPC‐GENE and TCGA‐PRAD to examine HLA alleles, antiviral T‐cell receptors and prostate cancer disease recurrence after prostatectomy. Carrying HLA‐A*02:01 (111/229; 48% of patients) was independently associated with disease recurrence in patients with low‐intermediate risk prostate cancer. HLA‐A*11 (carried by 42/441; 10% of patients) was independently associated with rapid disease recurrence in patients with high‐risk prostate cancer. Moreover, HLA‐A*02:01 carriers in which anti‐cytomegalovirus T‐cell receptors (CMV‐TCR) were identified in tumors (13/144; 10% of all patients in the cohort) had a higher risk of disease recurrence than CMV‐TCR‐negative patients. These findings suggest that HLA‐type and CMV immunity may be valuable biomarkers for prostate cancer progression.
In this study, we find that variants of genes that are essential for the immune system (HLA‐A*02:01 and HLA‐A*11) are associated with prostate cancer progression after radical prostatectomy. Local detection of immunity to cytomegalovirus, but not EBV or Influenza A, was associated with particularly low disease recurrence‐free survival, suggesting that HLA‐type and viral immunity could predict cancer progression.