美国纽约大学格罗斯曼医学院Dafna Bar-Sagi研究组发现运动诱导IL-15/IL-15Rα轴参与胰腺癌抗肿瘤免疫。相关论文于2022年6月2日发表于国际顶尖学术期刊《癌细胞》杂志上。
他们表明有氧运动通过调节全身和肿瘤内免疫来减少胰腺导管腺癌 (PDA)肿瘤的生长。从机制上讲，运动促进免疫动员和肿瘤浸润性 IL15Rα+ CD8 T 细胞的积累，这些细胞负责肿瘤保护作用。在临床样本中，还观察到肿瘤内 CD8 T 细胞的运动依赖性增加。强调白细胞介素 (IL)-15/IL-15Rα 轴的翻译潜力，IL-15 超激动剂 (NIZ985) 治疗可减弱肿瘤生长、延??长生存期并增强对化疗的敏感性。
最后，运动或 NIZ985 都可以使胰腺肿瘤对 αPD-1 敏感，从而提高抗肿瘤和生存获益。总的来说，他们的研究结果突出了运动肿瘤学轴的治疗潜力，并将 IL-15 激活确定为这种致命疾病的潜在治疗策略。
据介绍，有氧运动与降低癌症发病率和癌症相关死亡率有关。然而，关于运动对PDA的影响知之甚少，这是一种目前治疗选择有限的疾病。
附：英文原文
Title: Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer
Author: Emma Kurz, Carolina Alcantara Hirsch, Tanner Dalton, Sorin Alberto Shadaloey, Alireza Khodadadi-Jamayran, George Miller, Sumedha Pareek, Hajar Rajaei, Chirayu Mohindroo, Seyda Baydogan, An Ngo-Huang, Nathan Parker, Matthew H.G. Katz, Maria Petzel, Emily Vucic, Florencia McAllister, Keri Schadler, Rafael Winograd, Dafna Bar-Sagi
Issue&Volume: 2022-06-02
Abstract: Aerobic exercise is associated with decreased cancer incidence and cancer-associatedmortality. However, little is known about the effects of exercise on pancreatic ductaladenocarcinoma (PDA), a disease for which current therapeutic options are limited.Herein, we show that aerobic exercise reduces PDA tumor growth, by modulating systemicand intra-tumoral immunity. Mechanistically, exercise promotes immune mobilizationand accumulation of tumor-infiltrating IL15Rα+ CD8 T cells, which are responsible for the tumor-protective effects. In clinicalsamples, an exercise-dependent increase of intra-tumoral CD8 T cells is also observed.Underscoring the translational potential of the interleukin (IL)-15/IL-15Rα axis,IL-15 super-agonist (NIZ985) treatment attenuates tumor growth, prolongs survival,and enhances sensitivity to chemotherapy. Finally, exercise or NIZ985 both sensitizepancreatic tumors to αPD-1, with improved anti-tumor and survival benefits. Collectively,our findings highlight the therapeutic potential of an exercise-oncology axis andidentify IL-15 activation as a promising treatment strategy for this deadly disease.
DOI: 10.1016/j.ccell.2022.05.006
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00217-3
Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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