Peripheral natural killer cell and allo-stimulated T-cell function in kidney transplant recipients associate with cancer risk and immunosuppression-related complications

Christopher M. Hope, Alexander Troelnikov, William Hanf, Shilpanjali Jesudason, Patrick T. Coates, Peter S. Heeger, Robert P. Carroll

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Reducing immunosuppression has been proposed as a means of preventing cancer in kidney transplant recipients but this can precipitate graft rejection. Here we tested whether anti-tumor natural killer (NK) cell and allo-responsive T-cell function in kidney transplant recipients may predict cancer risk and define risk of rejection. NK cell function was measured by the release of lactate dehydrogenase and T-cell allo-response by interferon-γ quantification using a panel of reactive T-cell enzyme-linked immunospot (ELISPOT) in 56 kidney transplant recipients with current or past cancer and 26 kidney transplant recipients without cancer. NK function was significantly impaired and the allo-response was significantly lower in kidney transplant recipients with cancer. With prospective follow-up, kidney transplant recipients with poor NK cell function had a hazard ratio of 2.1 (95% confidence interval 0.97-5.00) for the combined end point of metastatic cancer, cancer-related death, or septic death. Kidney transplant recipients with low interferon-γ release were also more likely to reach this combined end point. Thus, posttransplant monitoring of allo-immunity and NK cell function is useful for assessing the risk of over immunosuppression for the development of malignancy and/or death from cancer or sepsis.

Original languageEnglish
Pages (from-to)1374-1382
Number of pages9
JournalKidney International
Volume88
Issue number6
DOIs
Publication statusPublished or Issued - 1 Dec 2015

Keywords

  • Cancer
  • IFN-γ ELISPOT
  • Immunosuppression
  • Kidney transplantation
  • NK cells

ASJC Scopus subject areas

  • Nephrology

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