Zeng Ziyang, Zhou Jian, Zhang Weili, Peng Jianhong, Li Yuan, Jin-Si-Han E-Er-Man-Bie-Ke, Wang Hao, Lian Shaopu, Feng Cheng, Xie Chuanmiao, Pan Zhizhong, Lu Zhenhai
Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Department of Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Front Immunol. 2025 May 30;16:1589869. doi: 10.3389/fimmu.2025.1589869. eCollection 2025.
Obesity and overweight have been suggested as a potential predictor of favorable outcomes in certain malignancies treated with immunotherapy. However, most studies have relied on BMI as a proxy for adiposity, without fully considering the distinct roles of fat and lean tissues. This study aimed to explore the association between body composition and treatment response in colorectal cancer patients receiving neoadjuvant PD-1 inhibitor therapy.
Patients with dMMR/MSI-H colorectal cancer undergoing neoadjuvant PD-1 blockade were included in this study. Body composition parameters were measured using baseline CT images. Pathological response was assessed using tumor regression grade (TRG). Univariate and multivariate analyses were performed to examine the association between body composition variables (total adipose tissue, visceral adipose tissue, subcutaneous adipose tissue, visceral-to-subcutaneous adipose tissue ratio, and skeletal muscle) and pathological complete response (pCR) rates. Correlation analysis was conducted to detect the relationship between body composition and lipid profiles.
A total of 84 patients were included in the analysis. Patients with poor treatment response exhibited significantly lower levels of visceral adipose tissue (VAT), total adipose tissue (TAT), and BMI. On multivariate analysis, higher VAT volume and elevated circulating lymphocyte count were independently associated with increased pCR rates. The positive association between VAT and treatment response was consistent across most subgroups except in patients aged ≥ 65, where the effect tended to be reversed. Additionally, VAT volume correlated positively with triglycerides and negatively with high-density lipoprotein cholesterol.
Higher visceral adipose tissue volume is associated with improved pathological complete response in dMMR/MSI-H colorectal cancer patients treated with PD-1 inhibitors. However, this favorable effect of visceral adiposity may be diminished or reversed in elderly patients (≥ 65 y), highlighting the potential influence of aging on the metabolic-immune interplay in immunotherapy response.
肥胖和超重被认为是接受免疫治疗的某些恶性肿瘤预后良好的潜在预测指标。然而，大多数研究依赖体重指数（BMI）作为肥胖的替代指标，而没有充分考虑脂肪组织和瘦组织的不同作用。本研究旨在探讨接受新辅助PD-1抑制剂治疗的结直肠癌患者的身体组成与治疗反应之间的关联。
本研究纳入了接受新辅助PD-1阻断治疗的错配修复缺陷（dMMR）/微卫星高度不稳定（MSI-H）结直肠癌患者。使用基线CT图像测量身体组成参数。使用肿瘤退缩分级（TRG）评估病理反应。进行单因素和多因素分析，以检验身体组成变量（总脂肪组织、内脏脂肪组织、皮下脂肪组织、内脏与皮下脂肪组织比值和骨骼肌）与病理完全缓解（pCR）率之间的关联。进行相关性分析以检测身体组成与血脂谱之间的关系。
共有84例患者纳入分析。治疗反应较差的患者内脏脂肪组织（VAT）、总脂肪组织（TAT）和BMI水平显著较低。多因素分析显示，较高的VAT体积和循环淋巴细胞计数升高与pCR率增加独立相关。除年龄≥65岁的患者外，VAT与治疗反应之间的正相关在大多数亚组中是一致的，在该组中这种效应趋于相反。此外，VAT体积与甘油三酯呈正相关，与高密度脂蛋白胆固醇呈负相关。
在接受PD-1抑制剂治疗的dMMR/MSI-H结直肠癌患者中，较高的内脏脂肪组织体积与改善的病理完全缓解相关。然而，内脏肥胖的这种有利作用在老年患者（≥65岁）中可能会减弱或逆转，这突出了衰老对免疫治疗反应中代谢-免疫相互作用的潜在影响。
