Modulation of NKG2D, NKp46, and Ly49C/I facilitates natural killer cell-mediated control of lung cancer

Author:

Shi Lei,Li Kang,Guo Yizhan,Banerjee Anirban,Wang Qing,Lorenz Ulrike M.ORCID,Parlak Mahmut,Sullivan Lucy C.,Onyema Oscar Okwudiri,Arefanian Saeed,Stelow Edward B.,Brautigan David L.,Bullock Timothy N. J.,Brown Michael G.,Krupnick Alexander Sasha

Abstract

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.

Funder

U.S. Department of Veterans Affairs

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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