UNLABELLED: Several immune suppressive mechanisms that evade the host immune response have been described in patients with hepatocellular carcinoma (HCC); one of these mechanisms is expansion of myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to inhibit T cell responses in tumor-bearing mice, but little is known about these cells in humans. Here, we have analyzed and characterized the effect of MDSCs on the innate immune system, in particular, their interaction with natural killer (NK) cells in patients with HCC. MDSCs from patients with HCC inhibited autologous NK cell cytotoxicity and cytokine secretion when cultured together in vitro. This suppression was dependent on cell contact, but did not rely on the arginase activity of MDSCs, which is a hallmark function of these cells. However, MDSC-mediated inhibition of NK cell function was dependent mainly on the NKp30 on NK cells. CONCLUSION: Our study suggests a new role for MDSCs in patients with HCC in disarming the innate immune system and further contributing to the immune suppressor network in these patients. These findings have important implications when designing immunotherapy protocols.
UNLABELLED: Several immune suppressive mechanisms that evade the host immune response have been described in patients with hepatocellular carcinoma (HCC); one of these mechanisms is expansion of myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to inhibit T cell responses in tumor-bearing mice, but little is known about these cells in humans. Here, we have analyzed and characterized the effect of MDSCs on the innate immune system, in particular, their interaction with natural killer (NK) cells in patients with HCC. MDSCs from patients with HCC inhibited autologous NK cell cytotoxicity and cytokine secretion when cultured together in vitro. This suppression was dependent on cell contact, but did not rely on the arginase activity of MDSCs, which is a hallmark function of these cells. However, MDSC-mediated inhibition of NK cell function was dependent mainly on the NKp30 on NK cells. CONCLUSION: Our study suggests a new role for MDSCs in patients with HCC in disarming the innate immune system and further contributing to the immune suppressor network in these patients. These findings have important implications when designing immunotherapy protocols.
Authors: Azadeh Arabzadeh; Jeremy Dupaul-Chicoine; Valérie Breton; Sina Haftchenary; Sara Yumeen; Claire Turbide; Maya Saleh; Kevin McGregor; Celia M T Greenwood; Uri David Akavia; Richard S Blumberg; Patrick T Gunning; Nicole Beauchemin Journal: Gut Date: 2015-02-09 Impact factor: 23.059
Authors: Suzanne Ostrand-Rosenberg; Pratima Sinha; Daniel W Beury; Virginia K Clements Journal: Semin Cancer Biol Date: 2012-02-01 Impact factor: 15.707
Authors: David Vasquez-Dunddel; Fan Pan; Qi Zeng; Mikhail Gorbounov; Emilia Albesiano; Juan Fu; Richard L Blosser; Ada J Tam; Tullia Bruno; Hao Zhang; Drew Pardoll; Young Kim Journal: J Clin Invest Date: 2013-04 Impact factor: 14.808