Cytomegalovirus exposure, immune exhaustion and cancer occurrence in renal transplant recipients

Transpl Int. 2012 Sep;25(9):948-55. doi: 10.1111/j.1432-2277.2012.01521.x. Epub 2012 Jul 11.

Abstract

The role of Cytomegalovirus (CMV) in carcinogenesis is controversial. We studied whether CMV may contribute to cancer occurrence in renal transplant recipients. We studied a prospective cohort of 455 consecutive patients who received a kidney transplant between January 1995 and December 2006. All cancers and types of cancers were assessed. Lymphocyte phenotype and cytokines production were analysed according to CMV status in a subset population of this cohort. Mean follow-up was 84 ± 29 months. One hundred and nineteen cancers (26.2%) occurred during the study follow-up. There was a higher cumulated incidence of cancers in CMV-exposed patients (30.4% vs. 20%; P=0.018). Mean time to cancer occurrence was shorter in CMV-exposed patients than in CMV-naïve patients (4.7 ± 2.6 vs. 6.7 ± 2.8; P = 0.001). Cox regression analysis revealed that both pretransplant CMV exposure (HR, 1.83; 95% CI, 1.17-2.88; P = 0.009) and post-transplant CMV replication (HR, 2.17; 95% CI, 1.02-4.59; P = 0.044) were risk factors for cancer. Among CD8+ T cells, exhausted T cells assessed as CD57+CD28- were expanded in CMV-exposed patients (26 ± 20 vs. 9 ± 8%; P < 0.0001), whereas CD8+CD57+IL2- cells were more frequent in CMV-exposed patients. Our results highly suggest that CMV increases the risk of cancer after transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD28 Antigens / biosynthesis
  • CD57 Antigens / biosynthesis
  • Cohort Studies
  • Cytomegalovirus / metabolism*
  • Female
  • Humans
  • Immune System
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neoplasms / immunology*
  • Neoplasms / virology
  • Phenotype
  • Prospective Studies
  • Regression Analysis
  • Renal Insufficiency / complications
  • Renal Insufficiency / therapy*
  • Renal Insufficiency / virology
  • Risk
  • Treatment Outcome

Substances

  • CD28 Antigens
  • CD57 Antigens