Natural Killer Lymphocytes Are Dysfunctional in Kidney Transplant Recipients On Diagnosis of Cancer.

Abstract

Background: Cancer incidence is increased after kidney transplantation. Natural Killer (NK) cells are key effectors of the tumor immune response through activating receptors. In assessing immunological characteristics of T and NK cells from kidney transplant recipients (KTRs) who develop cancer, we found important deficiencies in NK cells. Patients and Methods: We conducted a prospective multicentre matched case-control study including 42 KTRs on diagnosis of cancer and 41 KTRs without cancer. Extensive phenotyping of T and NK cells populations was performed. Functional tests of NK cells were performed in a subset of patients. Results: KTRs with cancer had a significantly higher incidence of both acute rejection (P=0.02) and CMV infection (P=0.03) than matched controls. First, KTRs with cancer had more lymphopenia than control KTR (1020/mm3+/-32 vs 1218/mm3+/-34; P=0.001) including a significant CD4+ lymphopenia (P=0.01). Total CD3-/CD56+ NK cell counts were similar in KTRs with or without cancer. However, KTRs with cancer had a much lower frequency of the cytokine-enriched CD56bright NK cell subset (P=0.001), and consequently a higher CD56dim/bright ratio (P=0.005). The percentage of NK cells expressing NKp46 was decreased in KTRs with cancer both for all NK cells (44% vs 58%, P=0.01) and for CD56dim and CD56bright subsets. Furthermore, the NK cells showed functional deficiencies. The ability of NK cells to degranulate CD107a+ cytolytic vesicles was reduced in KTRs with cancer (11% vs 22% in control patients; P=0.01). In addition the percentage of NK cells secreting IFNg was decreased (7.5% in KTRs with cancer vs 28.8% in the control group; P=0.01). Conclusion: These results reveal an imbalance between NK cell subpopulations and functional NK defects in KTRs at the onset of malignancy. There was a decreased number of NK cells producing INFg. This study highlights the role of NKp46. Decreased expression of NKp46 may contribute to the initiation of malignancies. NKp46 could be considered as a potentially valuable marker during immunological follow-up of KTRss.