Abstract
Natural killer (NK) cells are cytotoxic lymphocytes that are able to kill tumor cells without prior sensitization. It has been shown that NK cells play a pivotal role in a variety of cancers, highlighting their relevance in tumor immunosurveillance. NK cell infiltration has been reported in renal cell carcinoma (RCC), the most frequent kidney cancer in adults, and their presence has been associated with patients’ survival. However, the role of NK cells in this disease is not yet fully understood. In this review, we summarize the biology of NK cells and the mechanisms through which they are able to recognize and kill tumor cells. Furthermore, we discuss the role that NK cells play in renal cell carcinoma, and review current strategies that are being used to boost and exploit their cytotoxic capabilities.
Highlights
Natural killer (NK) cells are large granular lymphocytes that were described more than 40 years ago [1,2]
In addition to the important role of NK cells in the development of an adequate immune response against tumors and pathogens, it is essential to maintain tolerance towards the host. This is achieved through a process called education or licensing, which is governed by the interaction of inhibitory receptors (KIR, Ly49, and CD94/NKG2A) with their ligands, the major histocompatibility complex (MHC) class I molecules, during NK cell development [69,70,71,72,73]
Results have shown that human anti-Carbonic anhydrase IX (CAIX) monoclonal antibody (mAb) induce NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) against renal cell carcinoma (RCC) cells
Summary
Natural killer (NK) cells are large granular lymphocytes that were described more than 40 years ago [1,2]. NK and ILC1 cells have a very similar phenotype, as well as similar effector functions, especially in relation to the pattern of cytokines that they secrete, which is mainly IFNγ They differ in that ILC1 exhibits very little or no cytotoxic activity due to the low or zero levels of perforin and granzymes they express. The CD56dim subset expresses low levels of the receptor, constitutes 90–95% of circulating NK cells, and is characterized by increased cytotoxic activity against targets and a lower capacity for cytokine production, such as IFNγ, in response to stimulation with interleukins such as IL-2, IL-12, IL-15, and IL-18. Single cell transcriptomics studies have revealed tissue-specific gene signatures that allow identification of NK cell populations that differ between tissues [41,42]
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