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

Mol Oncol. 2022 Oct;16(19):3452-3464. doi: 10.1002/1878-0261.13273. Epub 2022 Aug 31.

Abstract

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.

Keywords: HLA-alleles; T-cells; antiviral protection; cytomegalovirus (CMV); prognosis; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents
  • Cytomegalovirus
  • Cytomegalovirus Infections* / genetics
  • HLA-A Antigens
  • Humans
  • Male
  • Neoplasm Recurrence, Local / genetics
  • Prostatectomy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / surgery
  • Receptors, Antigen, T-Cell / genetics

Substances

  • Antiviral Agents
  • HLA-A Antigens
  • Receptors, Antigen, T-Cell

Associated data

  • RefSeq/NC_006273.2