Browsing by Author "Larsen, Annette K. (7201649525)"

NK cells are important effectors of innate immunity that mount the first line of defense toward tumor growth. Interleukin-4 (IL-4) has recently been shown to regulate NK cell function, although its role in the regulation of NK cell function in cancer patients has not been clarified. The aim of this study was to investigate the effect of IL-4 on the function and the receptor characteristics of CD16-defined NK cells and their cytotoxic CD16bright and regulatory CD16dim subsets. Peripheral blood lymphocytes obtained from 36 metastatic melanoma (MM) patients treated for 18 h with 10 ng/mL IL-4 were evaluated for NK cell cytotoxicity using the radioactive 51chromium release assay. Expression of the activating receptors NKG2D and CD161, as well as the inhibitory receptors CD158a and CD158b, was analyzed on CD3-CD16+ NK cells and their subsets by flow cytometry. IL-4 induced significant in vitro enhancement of NK cell activity, as well as increased expression of the CD107a degranulation marker, by CD3-CD16dim NK cells. NKG2D expression was also increased on CD3-CD16+ cells by IL-4 with no alteration of the expression of CD161 and inhibitory KIR receptors. Although in vitro treatment with IL-4 increased both the expression of NKG2D and the cytotoxicity of NK cells, it had no detectable effect on the transcription of the TGF-β gene in NK cells of MM patients. The IL-4-induced NK cell cytotoxicity and increased activating NKG2D receptor expression may indicate an important antitumor effect of IL-4 with a potential application for immunotherapy of MM patients. © 2020, JLE/Springer.

NK cells are important effectors of innate immunity that mount the first line of defense toward tumor growth. Interleukin-4 (IL-4) has recently been shown to regulate NK cell function, although its role in the regulation of NK cell function in cancer patients has not been clarified. The aim of this study was to investigate the effect of IL-4 on the function and the receptor characteristics of CD16-defined NK cells and their cytotoxic CD16bright and regulatory CD16dim subsets. Peripheral blood lymphocytes obtained from 36 metastatic melanoma (MM) patients treated for 18 h with 10 ng/mL IL-4 were evaluated for NK cell cytotoxicity using the radioactive 51chromium release assay. Expression of the activating receptors NKG2D and CD161, as well as the inhibitory receptors CD158a and CD158b, was analyzed on CD3-CD16+ NK cells and their subsets by flow cytometry. IL-4 induced significant in vitro enhancement of NK cell activity, as well as increased expression of the CD107a degranulation marker, by CD3-CD16dim NK cells. NKG2D expression was also increased on CD3-CD16+ cells by IL-4 with no alteration of the expression of CD161 and inhibitory KIR receptors. Although in vitro treatment with IL-4 increased both the expression of NKG2D and the cytotoxicity of NK cells, it had no detectable effect on the transcription of the TGF-β gene in NK cells of MM patients. The IL-4-induced NK cell cytotoxicity and increased activating NKG2D receptor expression may indicate an important antitumor effect of IL-4 with a potential application for immunotherapy of MM patients. © 2020, JLE/Springer.

Natural killer (NK) cells are innate lymphoid cells that are important effectors in the first line of defense toward transformed cells. This is mediated both by direct cytotoxic mechanisms and by production of immunoregulatory cytokines. Recent evidence has shown that NK cells also display memory, similar to the cells of the adaptive immune system. Cytokines are pivotal for the maturation, activation and survival of NK cells. Interleukins (IL)-2, IL-12, IL-15, IL-18, IL-21 and type I interferons positively regulate NK cell function, either independently or in cooperation, whereas other cytokines, such as IL-23 and IL-27, may enhance or suppress NK cell function depending on the context. In the tumor microenvironment, TGFβ, IL-10 and IL-6 suppress NK cell activity not only directly, but also indirectly, by affecting immunosuppressive cells and by antagonizing the effect of stimulatory cytokines, thereby dampening the antitumor response of NK cells and promoting subsequent tumor evasion and progression. Increased understanding of the NK cell response to cytokines has provided a better understanding of their impaired function in tumors which may aid in the development of novel immunotherapeutic strategies to enhance NK cell responses in cancer patients. © 2019 Elsevier Ltd

Natural killer (NK) cells are innate lymphoid cells that are important effectors in the first line of defense toward transformed cells. This is mediated both by direct cytotoxic mechanisms and by production of immunoregulatory cytokines. Recent evidence has shown that NK cells also display memory, similar to the cells of the adaptive immune system. Cytokines are pivotal for the maturation, activation and survival of NK cells. Interleukins (IL)-2, IL-12, IL-15, IL-18, IL-21 and type I interferons positively regulate NK cell function, either independently or in cooperation, whereas other cytokines, such as IL-23 and IL-27, may enhance or suppress NK cell function depending on the context. In the tumor microenvironment, TGFβ, IL-10 and IL-6 suppress NK cell activity not only directly, but also indirectly, by affecting immunosuppressive cells and by antagonizing the effect of stimulatory cytokines, thereby dampening the antitumor response of NK cells and promoting subsequent tumor evasion and progression. Increased understanding of the NK cell response to cytokines has provided a better understanding of their impaired function in tumors which may aid in the development of novel immunotherapeutic strategies to enhance NK cell responses in cancer patients. © 2019 Elsevier Ltd