Qiwei Zhang1, Weiwei Rui2, Yongsheng Jiang3, Fei Yuan2, Yong Chen4, Xiaoxia Guo1, Yu Zhou1, Zhiyuan Wu5, Chaofu Wang6, Xiaoyi Ding7. 1. Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China. 2. Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China. 3. Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. 4. Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China. 5. Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China. wuzhiyuan@shsmu.edu.cn. 6. Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China. wcf11956@rjh.com.cn. 7. Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China. dxy10456@rjh.com.cn.
Abstract
PURPOSE: OX40 signaling pathway occupies a vital place in anti-tumor immunity; however, the role of tumor-infiltrating OX40+ lymphocytes in pancreatic ductal adenocarcinoma (PDAC) remains to be identified. METHODS: A total of 325 sequential PDAC patients who received curative tumor resection between January 2014 and December 2016 were enrolled. Tissues of these patients were immunohistochemically assessed for tumor infiltration of CD4+ T cells, CD8+ cytotoxic T cells (CTLs), and OX40+ lymphocytes. The frequency of OX40+ tumor-infiltrating lymphocytes (TILs) was then analyzed to various clinicopathological features, densities of tumor infiltration of CD4+ T cells and CTLs, and survival analysis was conducted using Kaplan-Meier (KM) curves. The risk scores of associated markers were calculated by the Cox proportional-hazards model. RESULTS: Our results showed that higher OX40+ lymphocytes infiltration was significantly correlated with superior median overall survival (OS) (25.8 vs 13.4 months, P < 0.001). Additionally, using univariate and multivariate Cox proportional hazards analyses, this study revealed that together with tumor differentiation, tumor size, serum CA199 levels, serum CA125 levels, and the infiltration of intratumoral CD8+ T cells. The abundance of OX40+ lymphocytes within the tumor was continued to be an independent predictor for OS (P = 0.023, HR = 0.713, 95% CI: 0.532-0.954). CONCLUSIONS: This study demonstrated that intratumoral infiltration by a high number of OX40+ lymphocytes is a novel biomarker for favorable prognosis in resected PDAC patients, which implies that OX40-agonist-based immunotherapy might be a potential target in PDAC patients.
PURPOSE: OX40 signaling pathway occupies a vital place in anti-tumor immunity; however, the role of tumor-infiltrating OX40+ lymphocytes in pancreatic ductal adenocarcinoma (PDAC) remains to be identified. METHODS: A total of 325 sequential PDAC patients who received curative tumor resection between January 2014 and December 2016 were enrolled. Tissues of these patients were immunohistochemically assessed for tumor infiltration of CD4+ T cells, CD8+ cytotoxic T cells (CTLs), and OX40+ lymphocytes. The frequency of OX40+ tumor-infiltrating lymphocytes (TILs) was then analyzed to various clinicopathological features, densities of tumor infiltration of CD4+ T cells and CTLs, and survival analysis was conducted using Kaplan-Meier (KM) curves. The risk scores of associated markers were calculated by the Cox proportional-hazards model. RESULTS: Our results showed that higher OX40+ lymphocytes infiltration was significantly correlated with superior median overall survival (OS) (25.8 vs 13.4 months, P < 0.001). Additionally, using univariate and multivariate Cox proportional hazards analyses, this study revealed that together with tumor differentiation, tumor size, serum CA199 levels, serum CA125 levels, and the infiltration of intratumoral CD8+ T cells. The abundance of OX40+ lymphocytes within the tumor was continued to be an independent predictor for OS (P = 0.023, HR = 0.713, 95% CI: 0.532-0.954). CONCLUSIONS: This study demonstrated that intratumoral infiltration by a high number of OX40+ lymphocytes is a novel biomarker for favorable prognosis in resected PDAC patients, which implies that OX40-agonist-based immunotherapy might be a potential target in PDAC patients.
Authors: Thierry Conroy; Françoise Desseigne; Marc Ychou; Olivier Bouché; Rosine Guimbaud; Yves Bécouarn; Antoine Adenis; Jean-Luc Raoul; Sophie Gourgou-Bourgade; Christelle de la Fouchardière; Jaafar Bennouna; Jean-Baptiste Bachet; Faiza Khemissa-Akouz; Denis Péré-Vergé; Catherine Delbaldo; Eric Assenat; Bruno Chauffert; Pierre Michel; Christine Montoto-Grillot; Michel Ducreux Journal: N Engl J Med Date: 2011-05-12 Impact factor: 91.245
Authors: Anand Mahadevan; Rebecca Miksad; Michael Goldstein; Ryan Sullivan; Andrea Bullock; Elizabeth Buchbinder; Douglas Pleskow; Mandeep Sawhney; Tara Kent; Charles Vollmer; Mark Callery Journal: Int J Radiat Oncol Biol Phys Date: 2011-06-12 Impact factor: 7.038
Authors: Devin Schellenberg; Jeff Kim; Claudia Christman-Skieller; Carlene L Chun; Laurie Ann Columbo; James M Ford; George A Fisher; Pamela L Kunz; Jacques Van Dam; Andrew Quon; Terry S Desser; Jeffrey Norton; Annie Hsu; Peter G Maxim; Lei Xing; Karyn A Goodman; Daniel T Chang; Albert C Koong Journal: Int J Radiat Oncol Biol Phys Date: 2011-05-05 Impact factor: 7.038