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

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 endpoint 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 endpoint. Thus, post-transplant 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.

TNF-α Production by Monocytes Stimulated With Epstein-Barr Virus–Peptides as a Marker of Immunosuppression-Related Adverse Events in Kidney Transplant Recipients

“…PPV and NPV depend on prevalence of the disease in the studied population. Considering that the proportion of OIS patients in this cohort (33%, 24 of 71) is encountered also in real-life settings, 20 present PPV and NPV values are not biased by an unexpected frequency of the event. In this respect, the validated NPV is at a level similar to what led previous diagnostic tests, such as B-type natriuretic peptide, to be translated into clinical practice 21 .…”

The Role of the Immune System in Cutaneous Squamous Cell Carcinoma

“…NK cells play a critical role in suppressing cSCC development in murine models [39], though the TME may modulate their cytotoxicity through downregulation of activating receptors [53]. Genetic or acquired impaired function or reduced number of NK cells is associated with increased risk of herpesvirus, papillomavirus, and cSCC in humans [54,55,56,57]. This indicates that NK cells play a key role in immunosurveillance against cSCC development.…”

Role of novel biomarkers in kidney transplantation

“…Hope et al[ 83 ] in their study of 82 KTRs (56 with known malignancy, 26 without) found that weak NK cell activity, derived from lactate dehydrogenase and interferon-gamma quantification using reactive T-cell enzyme-linked immunospot, was associated with metastatic cancer, cancer-related death, or septic death [HR = 2.1 (95%CI: 0.97 to 5.00)][ 83 ].…”