PURPOSE: In uveal melanoma, low human leukocyte antigen (HLA) class I expression on primary tumors is associated with a decreased risk of metastasis. Consequently, it has been suggested that natural killer (NK) cells, which detect decreased expression of HLA class I, are involved in the immune control of metastases. In this study, three novel lines of evidence were identified that support a role for NK cells. METHODS: Uveal melanoma cell lines were used to determine the expression of NK cell receptor ligands (MICA, MICB, ULBP1-3, CD112, CD155, and HLA class I) and to examine sensitivity to lysis by human NK cell lines. Because interactions between polymorphic killer immunoglobulin receptors (KIRs) and HLA regulate NK cell function, KIR and HLA genotyping was performed on 154 patients with uveal melanoma and 222 healthy control subjects. RESULTS: First, all 11 uveal melanoma cell lines tested expressed ligands for activating as well as inhibitory NK cell receptors. Second, such cell lines were lysed efficiently by human NK cells in vitro. Finally, the HLA-C genotype was related to the risk of metastasis-related death in patients with uveal melanoma: The patients carrying HLA-C alleles encoding ligands for KIR2DL1 and KIR2DL2/3 (HLA-C group 1/group 2 heterozygous patients), both inhibitory NK receptors, had a longer metastasis-free survival than did those carrying HLA-C ligands for either KIR2DL1 (HLA-C group 2 homozygotes) or KIR2DL2/3 (HLA-C group 1 homozygotes). CONCLUSIONS: Together, the data support a role for NK cells in the prevention of uveal melanoma metastases.
PURPOSE: In uveal melanoma, low human leukocyte antigen (HLA) class I expression on primary tumors is associated with a decreased risk of metastasis. Consequently, it has been suggested that natural killer (NK) cells, which detect decreased expression of HLA class I, are involved in the immune control of metastases. In this study, three novel lines of evidence were identified that support a role for NK cells. METHODS:Uveal melanoma cell lines were used to determine the expression of NK cell receptor ligands (MICA, MICB, ULBP1-3, CD112, CD155, and HLA class I) and to examine sensitivity to lysis by human NK cell lines. Because interactions between polymorphic killer immunoglobulin receptors (KIRs) and HLA regulate NK cell function, KIR and HLA genotyping was performed on 154 patients with uveal melanoma and 222 healthy control subjects. RESULTS: First, all 11 uveal melanoma cell lines tested expressed ligands for activating as well as inhibitory NK cell receptors. Second, such cell lines were lysed efficiently by human NK cells in vitro. Finally, the HLA-C genotype was related to the risk of metastasis-related death in patients with uveal melanoma: The patients carrying HLA-C alleles encoding ligands for KIR2DL1 and KIR2DL2/3 (HLA-C group 1/group 2 heterozygous patients), both inhibitory NK receptors, had a longer metastasis-free survival than did those carrying HLA-C ligands for either KIR2DL1 (HLA-C group 2 homozygotes) or KIR2DL2/3 (HLA-C group 1 homozygotes). CONCLUSIONS: Together, the data support a role for NK cells in the prevention of uveal melanoma metastases.
Authors: Jason J Luke; Pierre L Triozzi; Kyle C McKenna; Erwin G Van Meir; Jeffrey E Gershenwald; Boris C Bastian; J Silvio Gutkind; Anne M Bowcock; Howard Z Streicher; Poulam M Patel; Takami Sato; Jeffery A Sossman; Mario Sznol; Jack Welch; Magdalena Thurin; Sara Selig; Keith T Flaherty; Richard D Carvajal Journal: Pigment Cell Melanoma Res Date: 2014-09-01 Impact factor: 4.693
Authors: José A Campillo; Isabel Legaz; M Rocío López-Álvarez; José Miguel Bolarín; Beatriz Las Heras; Manuel Muro; Alfredo Minguela; María R Moya-Quiles; Rosa Blanco-García; Helios Martínez-Banaclocha; Ana M García-Alonso; M Rocío Alvarez-López; Jorge A Martínez-Escribano Journal: Immunogenetics Date: 2013-01-31 Impact factor: 2.846
Authors: Susan Achberger; Wayne Aldrich; Raymond Tubbs; John W Crabb; Arun D Singh; Pierre L Triozzi Journal: Mol Immunol Date: 2013-12-25 Impact factor: 4.407
Authors: Mariette Labots; Kristy J Gotink; Henk Dekker; Kaamar Azijli; Johannes C van der Mijn; Charlotte M Huijts; Sander R Piersma; Connie R Jiménez; Henk M W Verheul Journal: Exp Mol Med Date: 2016-12-16 Impact factor: 8.718