• 在肥胖小鼠及肥胖人体中,PD1+ T细胞比例增加,Ki67+ T细胞比例降低;
  • 瘦素部分介导了上述现象,并与PD-1表达水平相关;
  • 肥胖可促进肿瘤细胞生长和T细胞耗竭;
  • 在荷瘤小鼠中,肥胖增强了PD-1单抗的治疗效果,减少了肿瘤的体积及转移;
  • 在152名临床癌症患者(其中39名BMI≥30)中,肥胖与PD-1/PD-L1单抗的疗效增强有关,肥胖患者的无进展生存期及总生存期更长;
  • 肥胖对癌症具有矛盾效应,或可作为一些癌症免疫疗法的生物标志物。
Nature Medicine上发表的一项最新研究,发现肥胖在癌症治疗中的矛盾效应:肥胖可促进肿瘤细胞的增长,但在使用PD-1/PD-L1单抗治疗时,肥胖患者表现出了更长的无进展生存期及总生存期。
Nature Medicine [IF:87.241]

Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade



2018-11-12, Article

Abstract & Authors:展开

The recent successes of immunotherapy have shifted the paradigm in cancer treatment, but because only a percentage of patients are responsive to immunotherapy, it is imperative to identify factors impacting outcome. Obesity is reaching pandemic proportions and is a major risk factor for certain malignancies, but the impact of obesity on immune responses, in general and in cancer immunotherapy, is poorly understood. Here, we demonstrate, across multiple species and tumor models, that obesity results in increased immune aging, tumor progression and PD-1-mediated T cell dysfunction which is driven, at least in part, by leptin. However, obesity is also associated with increased efficacy of PD-1/PD-L1 blockade in both tumor-bearing mice and clinical cancer patients. These findings advance our understanding of obesity-induced immune dysfunction and its consequences in cancer and highlight obesity as a biomarker for some cancer immunotherapies. These data indicate a paradoxical impact of obesity on cancer. There is heightened immune dysfunction and tumor progression but also greater anti-tumor efficacy and survival after checkpoint blockade which directly targets some of the pathways activated in obesity.

First Authors:
Ziming Wang,Ethan G Aguilar

Correspondence Authors:
William J Murphy

All Authors:
Ziming Wang,Ethan G Aguilar,Jesus I Luna,Cordelia Dunai,Lam T Khuat,Catherine T Le,Annie Mirsoian,Christine M Minnar,Kevin M Stoffel,Ian R Sturgill,Steven K Grossenbacher,Sita S Withers,Robert B Rebhun,Dennis J Hartigan-O'Connor,Gema Méndez-Lagares,Alice F Tarantal,R Rivkah Isseroff,Thomas S Griffith,Kurt A Schalper,Alexander Merleev,Asim Saha,Emanual Maverakis,Karen Kelly,Raid Aljumaily,Sami Ibrahimi,Sarbajit Mukherjee,Michael Machiorlatti,Sara K Vesely,Dan L Longo,Bruce R Blazar,Robert J Canter,William J Murphy,Arta M Monjazeb