Paradoxical effects of adiposity and inflammation on immunotherapy efficacy in gastric cancer: novel insights from real-world data.

IF 6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastric Cancer Pub Date : 2025-05-12 DOI:10.1007/s10120-025-01622-w

Li-Li Shen, Hua-Long Zheng, Zhi-Wei Zheng, Bin-Bin Xu, Zhen Xue, Jia-Lin, Qi-Yue Chen, Jian-Wei Xie, Ping Li, Chang-Ming Huang, Jian-Xian Lin, Chao-Hui Zheng

{"title":"Paradoxical effects of adiposity and inflammation on immunotherapy efficacy in gastric cancer: novel insights from real-world data.","authors":"Li-Li Shen, Hua-Long Zheng, Zhi-Wei Zheng, Bin-Bin Xu, Zhen Xue, Jia-Lin, Qi-Yue Chen, Jian-Wei Xie, Ping Li, Chang-Ming Huang, Jian-Xian Lin, Chao-Hui Zheng","doi":"10.1007/s10120-025-01622-w","DOIUrl":null,"url":null,"abstract":"Background: Emerging studies suggest obesity may improve PD-1/PD-L1 inhibitor efficacy, correlating with prolonged survival, known as the 'obesity paradox'. However, the impact of this paradox and obesity-related chronic inflammation on immunotherapy for advanced gastric cancer (AGC) has not received sufficient research.Methods: Between January 2018 and December 2021, patients receiving neoadjuvant therapy were categorized into two groups: combined immunotherapy (ICIs, n = 173) and neoadjuvant chemotherapy (NAC, n = 126). Visceral (VATI) and subcutaneous adipose tissue index (SATI) were obtained from pre-treatment CT images. The systemic immune-inflammation index (SII) was calculated as platelet count multiplied by the neutrophil-to-lymphocyte ratio.Results: The median age of patients was 64 years (IQR 56-69), with 219 (73.2%) males and 80 (26.8%) females. In the ICIs group, the VATI-High group showed significantly higher 3-year overall survival (OS) (p = 0.010) and disease-free survival (DFS) (p = 0.029). Similar results were observed in the SATI analysis (p < 0.05). Conversely, OS (p = 0.040) and DFS (p = 0.039) were significantly lower in the SII-High group. Both VATI and SATI were independent protective factors for OS and DFS, but the effect disappeared after adjustment for SII. SII was associated with poorer OS and DFS, even after adjustment for VATI and SATI. No significant differences were observed in the analysis of the NAC group.Conclusions: Elevated adiposity indices (VATI/SATI) and low SII correlate with survival benefit in ICI-treated AGC patients, and importantly, this paradoxical survival benefit is dependent on SII status. In contrast, no such benefit is observed in chemotherapy-alone cohorts.","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gastric Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10120-025-01622-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Emerging studies suggest obesity may improve PD-1/PD-L1 inhibitor efficacy, correlating with prolonged survival, known as the 'obesity paradox'. However, the impact of this paradox and obesity-related chronic inflammation on immunotherapy for advanced gastric cancer (AGC) has not received sufficient research.

Methods: Between January 2018 and December 2021, patients receiving neoadjuvant therapy were categorized into two groups: combined immunotherapy (ICIs, n = 173) and neoadjuvant chemotherapy (NAC, n = 126). Visceral (VATI) and subcutaneous adipose tissue index (SATI) were obtained from pre-treatment CT images. The systemic immune-inflammation index (SII) was calculated as platelet count multiplied by the neutrophil-to-lymphocyte ratio.

Results: The median age of patients was 64 years (IQR 56-69), with 219 (73.2%) males and 80 (26.8%) females. In the ICIs group, the VATI-High group showed significantly higher 3-year overall survival (OS) (p = 0.010) and disease-free survival (DFS) (p = 0.029). Similar results were observed in the SATI analysis (p < 0.05). Conversely, OS (p = 0.040) and DFS (p = 0.039) were significantly lower in the SII-High group. Both VATI and SATI were independent protective factors for OS and DFS, but the effect disappeared after adjustment for SII. SII was associated with poorer OS and DFS, even after adjustment for VATI and SATI. No significant differences were observed in the analysis of the NAC group.

Conclusions: Elevated adiposity indices (VATI/SATI) and low SII correlate with survival benefit in ICI-treated AGC patients, and importantly, this paradoxical survival benefit is dependent on SII status. In contrast, no such benefit is observed in chemotherapy-alone cohorts.

查看原文本刊更多论文

肥胖和炎症对胃癌免疫治疗效果的矛盾影响：来自现实世界数据的新见解。

背景：新的研究表明，肥胖可能提高PD-1/PD-L1抑制剂的疗效，与延长生存期相关，被称为“肥胖悖论”。然而，这种悖论和肥胖相关的慢性炎症对晚期胃癌（AGC）免疫治疗的影响尚未得到足够的研究。方法：2018年1月至2021年12月，接受新辅助治疗的患者分为两组：联合免疫治疗组（ICIs, n = 173）和新辅助化疗组（NAC, n = 126）。术前CT图像获得内脏（VATI）和皮下脂肪组织指数（SATI）。系统免疫炎症指数（SII）由血小板计数乘以中性粒细胞与淋巴细胞的比值计算。结果：患者中位年龄64岁（IQR 56 ~ 69），其中男性219例（73.2%），女性80例（26.8%）。在ICIs组中，vdi - high组的3年总生存期（OS）（p = 0.010）和无病生存期（DFS）（p = 0.029）显著高于ICIs组。结论：在接受ici治疗的AGC患者中，肥胖指数（VATI/SATI）升高和SII降低与生存获益相关，重要的是，这种矛盾的生存获益依赖于SII状态。相比之下，在单独化疗的队列中没有观察到这样的益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.