Chao Yang1,2,3,4, He Cheng1,2,3,4, Yiyin Zhang1,2,3,4, Kun Fan1,2,3,4, Guopei Luo1,2,3,4, Zhiyao Fan1,2,3,4, Qiuyi Huang1,2,3,4, Yu Lu1,2,3,4, Kaizhou Jin1,2,3,4, Zhengshi Wang1,2,3,4, Xianjun Yu5,6,7,8, Chen Liu9,10,11,12. 1. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Xuhui District, Shanghai, 200032, People's Republic of China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China. 3. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, People's Republic of China. 4. Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, People's Republic of China. 5. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Xuhui District, Shanghai, 200032, People's Republic of China. yuxianjun@fudanpci.org. 6. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China. yuxianjun@fudanpci.org. 7. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, People's Republic of China. yuxianjun@fudanpci.org. 8. Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, People's Republic of China. yuxianjun@fudanpci.org. 9. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Xuhui District, Shanghai, 200032, People's Republic of China. liuchen@fudanpci.org. 10. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China. liuchen@fudanpci.org. 11. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, People's Republic of China. liuchen@fudanpci.org. 12. Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, People's Republic of China. liuchen@fudanpci.org.
Abstract
INTRODUCTION: Natural killer cells (NK) are often believed to play a positive role in the antitumor immune response. However, this is not the case for patients with advanced pancreatic cancer. This study was performed to determine the unique subtype of "educated" NK cells and their prognostic value in patients with advanced pancreatic cancer. METHODS: We divided 378 eligible patients into a derivation cohort (September 2010 to December 2014, n = 239) and a validation cohort (January 2015 to April 2016, n = 139). Flow cytometry was performed to analyze NK cells. Enzyme-linked immunosorbent assay was used to detect interleukin-2 (IL-2), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. The Kaplan-Meier method and the Cox proportional hazards model were used. RESULTS: Survival analysis showed that a high density of NK cells accompanied by a high neutrophil-to-lymphocyte ratio was associated with reduced overall survival in both the derivation and validation cohorts. Multivariable analysis also showed that high NK infiltration (HR 1.45, 95% CI 1.17 to 1.79, p = 0.001) was an independent prognostic factor. In these patients, high NK infiltration was associated with reduced levels of IL-2, IFN-γ and TNF-α, although only IFN-γ reached statistical significance, which accounted for this unique phenomenon. DISCUSSION: Natural killer cells in patients with advanced pancreatic cancer are a unique subtype with anergic features. A high density of NKs predicts poor survival in these patients, possibly because an active inflammatory response and reduced secretion of IL-2, IFN-γ and TNF-α inhibit NK activation.
INTRODUCTION: Natural killer cells (NK) are often believed to play a positive role in the antitumor immune response. However, this is not the case for patients with advanced pancreatic cancer. This study was performed to determine the unique subtype of "educated" NK cells and their prognostic value in patients with advanced pancreatic cancer. METHODS: We divided 378 eligible patients into a derivation cohort (September 2010 to December 2014, n = 239) and a validation cohort (January 2015 to April 2016, n = 139). Flow cytometry was performed to analyze NK cells. Enzyme-linked immunosorbent assay was used to detect interleukin-2 (IL-2), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. The Kaplan-Meier method and the Cox proportional hazards model were used. RESULTS: Survival analysis showed that a high density of NK cells accompanied by a high neutrophil-to-lymphocyte ratio was associated with reduced overall survival in both the derivation and validation cohorts. Multivariable analysis also showed that high NK infiltration (HR 1.45, 95% CI 1.17 to 1.79, p = 0.001) was an independent prognostic factor. In these patients, high NK infiltration was associated with reduced levels of IL-2, IFN-γ and TNF-α, although only IFN-γ reached statistical significance, which accounted for this unique phenomenon. DISCUSSION: Natural killer cells in patients with advanced pancreatic cancer are a unique subtype with anergic features. A high density of NKs predicts poor survival in these patients, possibly because an active inflammatory response and reduced secretion of IL-2, IFN-γ and TNF-α inhibit NK activation.
Authors: Katalin Balázs; Zsuzsa S Kocsis; Péter Ágoston; Kliton Jorgo; László Gesztesi; Gyöngyi Farkas; Gábor Székely; Zoltán Takácsi-Nagy; Csaba Polgár; Géza Sáfrány; Zsolt Jurányi; Katalin Lumniczky Journal: Cancers (Basel) Date: 2022-06-22 Impact factor: 6.575
Authors: Rachel Elizabeth Ann Fincham; Francesca Romana Delvecchio; Michelle R Goulart; Joe Poe Sheng Yeong; Hemant M Kocher Journal: World J Gastroenterol Date: 2021-06-28 Impact factor: 5.742