转移部位少于4个的广泛期小细胞肺癌患者可通过重塑肿瘤微环境从免疫检查点抑制剂再挑战中获益

IF 6.2 Q1 IMMUNOLOGY
ImmunoTargets and Therapy Pub Date : 2024-10-26 eCollection Date: 2024-01-01 DOI:10.2147/ITT.S483093
Xiaoling Shang, Chenyue Zhang, Yuanyuan Lv, Xiaoxiao Zhang, Kaiyue Guo, Huijuan Li, Haiyong Wang
{"title":"转移部位少于4个的广泛期小细胞肺癌患者可通过重塑肿瘤微环境从免疫检查点抑制剂再挑战中获益","authors":"Xiaoling Shang, Chenyue Zhang, Yuanyuan Lv, Xiaoxiao Zhang, Kaiyue Guo, Huijuan Li, Haiyong Wang","doi":"10.2147/ITT.S483093","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) has prolonged survival in patients with extensive-stage small cell lung cancer (ES-SCLC) as first-line treatment. However, whether ICI rechallenge could bring survival benefit to patients with ES-SCLC following its failure as first-line treatment remains unknown. Therefore, we aim to address the issue and identify the cohort of patients that may derive such benefit.</p><p><strong>Methods: </strong>Patients with ES-SCLC from both the IMpower133 study and Shandong Cancer Hospital and Institute (shanzhong cohort) who failed first-line ICI were included. Kaplan Meier analysis was performed to compare overall survival (OS). Both univariate and multivariate Cox regression analyses were conducted to identify factors affecting survival. Tumor immune cell infiltration was evaluated by the CIBERSORT algorithm and detected by multiplex immunofluorescence (mIF).</p><p><strong>Results: </strong>A total of 125 ES-SCLC patients undergoing atezolizumab and 161 patients undergoing ICI as first-line treatment were recruited from IMpower133 and shanzhong cohort. Those receiving ICI rechallenge had a longer OS than those without in IMpower133 (<i>P</i> = 0.08) and shanzhong cohort (<i>P</i> = 0.013). In IMpower133 cohort, subgroup analyses found that patients with <4 metastatic sites derived more survival benefit from atezolizumab (<i>P</i> = 0.008). For patients with ES-SCLC harboring <4 metastatic sites, there was significant OS difference between atezolizumab versus non-atezolizumab as retreatment (<i>P</i> = 0.036). Moreover, for ES-SCLC patients with <4 metastatic sites, atezolizumab improved survival compared with non-atezolizumab (hazard ratio [HR]: 0.457; 95% CI: 0.256-0.817; <i>P</i> = 0.008). These findings were confirmed in shanzhong cohort. Those harboring <4 metastatic sites had fewer M2 macrophage and more CD4 naïve T cells infiltration, which was further confirmed by mIF of ES-SCLC samples from shanzhong cohort.</p><p><strong>Conclusion: </strong>Our study provides rationale for ICI rechallenge among ES-SCLC patients with <4 metastatic sites, suggesting beneficial outcome by reshaping TME.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523948/pdf/","citationCount":"0","resultStr":"{\"title\":\"Patients with Extensive-Stage Small Cell Lung Cancer Harboring Less Than 4 Metastatic Sites May Benefit from Immune Checkpoint Inhibitor Rechallenge by Reshaping Tumor Microenvironment.\",\"authors\":\"Xiaoling Shang, Chenyue Zhang, Yuanyuan Lv, Xiaoxiao Zhang, Kaiyue Guo, Huijuan Li, Haiyong Wang\",\"doi\":\"10.2147/ITT.S483093\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) has prolonged survival in patients with extensive-stage small cell lung cancer (ES-SCLC) as first-line treatment. However, whether ICI rechallenge could bring survival benefit to patients with ES-SCLC following its failure as first-line treatment remains unknown. Therefore, we aim to address the issue and identify the cohort of patients that may derive such benefit.</p><p><strong>Methods: </strong>Patients with ES-SCLC from both the IMpower133 study and Shandong Cancer Hospital and Institute (shanzhong cohort) who failed first-line ICI were included. Kaplan Meier analysis was performed to compare overall survival (OS). Both univariate and multivariate Cox regression analyses were conducted to identify factors affecting survival. Tumor immune cell infiltration was evaluated by the CIBERSORT algorithm and detected by multiplex immunofluorescence (mIF).</p><p><strong>Results: </strong>A total of 125 ES-SCLC patients undergoing atezolizumab and 161 patients undergoing ICI as first-line treatment were recruited from IMpower133 and shanzhong cohort. Those receiving ICI rechallenge had a longer OS than those without in IMpower133 (<i>P</i> = 0.08) and shanzhong cohort (<i>P</i> = 0.013). In IMpower133 cohort, subgroup analyses found that patients with <4 metastatic sites derived more survival benefit from atezolizumab (<i>P</i> = 0.008). For patients with ES-SCLC harboring <4 metastatic sites, there was significant OS difference between atezolizumab versus non-atezolizumab as retreatment (<i>P</i> = 0.036). Moreover, for ES-SCLC patients with <4 metastatic sites, atezolizumab improved survival compared with non-atezolizumab (hazard ratio [HR]: 0.457; 95% CI: 0.256-0.817; <i>P</i> = 0.008). These findings were confirmed in shanzhong cohort. Those harboring <4 metastatic sites had fewer M2 macrophage and more CD4 naïve T cells infiltration, which was further confirmed by mIF of ES-SCLC samples from shanzhong cohort.</p><p><strong>Conclusion: </strong>Our study provides rationale for ICI rechallenge among ES-SCLC patients with <4 metastatic sites, suggesting beneficial outcome by reshaping TME.</p>\",\"PeriodicalId\":30986,\"journal\":{\"name\":\"ImmunoTargets and Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-10-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523948/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ImmunoTargets and Therapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/ITT.S483093\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ImmunoTargets and Therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/ITT.S483093","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:免疫检查点抑制剂(ICIs)作为一线治疗可延长广泛期小细胞肺癌(ES-SCLC)患者的生存期。然而,ICI一线治疗失败后,ICI再挑战能否为ES-SCLC患者带来生存获益仍是未知数。因此,我们旨在解决这一问题,并确定可能从中获益的患者群体:方法:纳入IMpower133研究和山东省肿瘤医院及研究所(山中队列)中一线ICI治疗失败的ES-SCLC患者。采用卡普兰-梅耶尔分析比较总生存期(OS)。进行单变量和多变量Cox回归分析,以确定影响生存的因素。肿瘤免疫细胞浸润通过CIBERSORT算法进行评估,并通过多重免疫荧光(mIF)进行检测:从IMpower133和陕中队列中招募了125名接受阿特珠单抗治疗的ES-SCLC患者和161名接受ICI一线治疗的患者。在IMpower133队列(P = 0.08)和shanzhong队列(P = 0.013)中,接受ICI再挑战的患者的OS长于未接受ICI再挑战的患者。在IMpower133队列中,亚组分析发现P = 0.008)。对于ES-SCLC患者,P = 0.036)。此外,ES-SCLC 患者的 P = 0.008)。这些发现在陕中队列中得到了证实。结论:我们的研究为ES-SCLC患者ICI再挑战提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Patients with Extensive-Stage Small Cell Lung Cancer Harboring Less Than 4 Metastatic Sites May Benefit from Immune Checkpoint Inhibitor Rechallenge by Reshaping Tumor Microenvironment.

Background: Immune checkpoint inhibitors (ICIs) has prolonged survival in patients with extensive-stage small cell lung cancer (ES-SCLC) as first-line treatment. However, whether ICI rechallenge could bring survival benefit to patients with ES-SCLC following its failure as first-line treatment remains unknown. Therefore, we aim to address the issue and identify the cohort of patients that may derive such benefit.

Methods: Patients with ES-SCLC from both the IMpower133 study and Shandong Cancer Hospital and Institute (shanzhong cohort) who failed first-line ICI were included. Kaplan Meier analysis was performed to compare overall survival (OS). Both univariate and multivariate Cox regression analyses were conducted to identify factors affecting survival. Tumor immune cell infiltration was evaluated by the CIBERSORT algorithm and detected by multiplex immunofluorescence (mIF).

Results: A total of 125 ES-SCLC patients undergoing atezolizumab and 161 patients undergoing ICI as first-line treatment were recruited from IMpower133 and shanzhong cohort. Those receiving ICI rechallenge had a longer OS than those without in IMpower133 (P = 0.08) and shanzhong cohort (P = 0.013). In IMpower133 cohort, subgroup analyses found that patients with <4 metastatic sites derived more survival benefit from atezolizumab (P = 0.008). For patients with ES-SCLC harboring <4 metastatic sites, there was significant OS difference between atezolizumab versus non-atezolizumab as retreatment (P = 0.036). Moreover, for ES-SCLC patients with <4 metastatic sites, atezolizumab improved survival compared with non-atezolizumab (hazard ratio [HR]: 0.457; 95% CI: 0.256-0.817; P = 0.008). These findings were confirmed in shanzhong cohort. Those harboring <4 metastatic sites had fewer M2 macrophage and more CD4 naïve T cells infiltration, which was further confirmed by mIF of ES-SCLC samples from shanzhong cohort.

Conclusion: Our study provides rationale for ICI rechallenge among ES-SCLC patients with <4 metastatic sites, suggesting beneficial outcome by reshaping TME.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
16.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
期刊介绍: Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信