Mukherjee Sarbajit, Seager R J, Lee Yong Hee, Conroy Jeffrey M, Kalinski Pawel, Pabla Sarabjot
Department of Medicine, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, New York, NY 14206, USA.
Bioinformatics, OmniSeq, Inc., 700 Ellicott Street, Buffalo, NY 14203, USA.
J Pers Med. 2021 Dec 7;11(12):1324. doi: 10.3390/jpm11121324.
Recent epidemiological studies have shown that obesity, typically measured by increased body mass index (BMI), is associated with an increased risk of gastroesophageal adenocarcinoma (GEAC), but the contributing molecular and immune mechanisms remain unknown. Since obesity is known to promote chronic inflammation, we hypothesized that obesity leads to inflammation-related immune dysfunction, which can be reversed by immune-modulating therapy. To test our hypothesis, we examined the clinical and molecular data from advanced GEAC patients. To this end, 46 GEAC tumors were evaluated for biomarkers representing tumor inflammation, cell proliferation, and PD-L1 expression. A CoxPH regression model with potential co-variates, followed by pairwise post hoc analysis, revealed that inflammation in the GEAC tumor microenvironment is associated with improved overall survival, regardless of BMI. We also observed a significant association between cell proliferation and progression-free survival in overweight individuals who received immune-modulating therapy. In conclusion, our data confirm the role of the immune system in the natural course of GEAC and its responses to immunotherapies, but do not support the role of BMI as an independent clinically relevant biomarker in this group of patients.
最近的流行病学研究表明，肥胖通常以体重指数（BMI）升高来衡量，与胃食管腺癌（GEAC）风险增加有关，但相关的分子和免疫机制仍不清楚。由于已知肥胖会促进慢性炎症，我们推测肥胖会导致与炎症相关的免疫功能障碍，而免疫调节治疗可以逆转这种障碍。为了验证我们的假设，我们检查了晚期GEAC患者的临床和分子数据。为此，对46个GEAC肿瘤进行了评估，以检测代表肿瘤炎症、细胞增殖和PD-L1表达的生物标志物。采用具有潜在协变量的CoxPH回归模型，随后进行两两事后分析，结果显示，无论BMI如何，GEAC肿瘤微环境中的炎症与总体生存率提高相关。我们还观察到，接受免疫调节治疗的超重个体中，细胞增殖与无进展生存期之间存在显著关联。总之，我们的数据证实了免疫系统在GEAC自然病程及其对免疫治疗反应中的作用，但不支持BMI作为这组患者独立的临床相关生物标志物的作用。
