In a murine model system in which NK cells are the dominant cytotoxic effector cells, Shi and Li et al. show that host MHC-I expression reversibly affects NK cell functionality and is required for NK cells to control MHC-1+ lung cancer. NK cell licensing by environmental MHC-I through Ly49C/I led to upregulation of NKG2D and NKp46. Stimulation of NKG2D and NKp46 through stress ligands on tumor cells resulted in shedding of Ly49C/I, eliminating interference with tumor MHC-I. Bone marrow transplant from MHC-1+/+ mice to MHC-I-/- mice enhanced NK cell activation and control of MHC-I+ tumor growth, suggesting clinical applications for re-licensing NK cells.
Natural killer (NK) cells play a critical role in controlling malignancies. Susceptibility or resistance to lung cancer, for example, specifically depends on NK cell function. Nevertheless, intrinsic factors that control NK cell-mediated clearance of lung cancer are unknown. Here we report that NK cells exposed to exogenous major histocompatibility class I (MHCI) provide a significant immunologic barrier to the growth and progression of malignancy. Clearance of lung cancer is facilitated by up-regulation of NKG2D, NKp46, and other activating receptors upon exposure to environmental MHCI. Surface expression of the inhibitory receptor Ly49C/I, on the other hand, is down-regulated upon exposure to tumor-bearing tissue. We thus demonstrate that NK cells exhibit dynamic plasticity in surface expression of both activating and inhibitory receptors based on the environmental context. Our data suggest that altering the activation state of NK cells may contribute to immunologic control of lung and possibly other cancers.
Author Info: (1) The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710049, China. Department of Surgery, University of Virginia, Charlottesville, VA 22908. Carter Immunology C
Author Info: (1) The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710049, China. Department of Surgery, University of Virginia, Charlottesville, VA 22908. Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. (2) The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710049, China. Department of Surgery, University of Virginia, Charlottesville, VA 22908. Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. (3) Department of Surgery, University of Virginia, Charlottesville, VA 22908. Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. (4) Department of Surgery, University of Virginia, Charlottesville, VA 22908. Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. (5) Department of Surgery, University of Virginia, Charlottesville, VA 22908. Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. (6) Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908. (7) Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908. (8) Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia. (9) Department of Surgery, University of Virginia, Charlottesville, VA 22908. Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. (10) Department of Surgery, Washington University, St. Louis, MO 43110. (11) Department of Pathology, University of Virginia, Charlottesville, VA 22908. (12) Department of Pathology, University of Virginia, Charlottesville, VA 22908. (13) Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. Department of Pathology, University of Virginia, Charlottesville, VA 22908. (14) Carter Immunology Center, University of Virginia, Charlottesville, VA 22908. Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, VA 22908. (15) Department of Surgery, University of Virginia, Charlottesville, VA 22908; sashak@virginia.edu. Carter Immunology Center, University of Virginia, Charlottesville, VA 22908.
