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Bone metastasis attenuates efficacy of immune checkpoint inhibitors and displays cold immune characteristics in Non-small cell lung cancer

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收录情况： ◇ SCIE

作者：
Zhu Yan-Juan[1,2,3,4] * ; Chang Xue-Song[1,2] * ; Zhou Rui[1] ; Chen Ya-Dong[1,2] ; Ma Hao-Chuan[1] ; Xiao Zhen-Zhen[1,2] ; Qu Xin[1,2] ; Liu Yi-Hong[1,2] ; Liu Li-Rong[1,2] ; Li Yong[1,2] ; Yu Ya-Ya[1,2] ; Zhang Hai-Bo[1,2,3,4,*1] ;
机构： [1]Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China [2]Department of Oncology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China [3]Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China [4]Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China
出处：
DOI： 10.1016/j.lungcan.2022.03.006
ISSN：

关键词： Non-small cell lung cancer Bone metastasis Immune checkpoint inhibitor Tumor immune micro-environment

摘要：
This study aimed to assess the clinical characteristics affecting outcomes after immune checkpoint inhibitors (ICI) therapies in non-small cell lung cancer (NSCLC) patients, and the underlying mechanism in tumor immune micro-environment (TIME).A total of 144 patients treated with ICI-based strategies were retrospectively analyzed. Expression of 10 immune antibodies in tumor tissues from other 60 untreated NSCLC patients were sequentially tested using multiplexed immunofluorescence (mIF) staining method. Correlation of clinical characteristics with ICI treatment outcomes and TIME characteristics were analyzed.Multivariate logistic and cox regression indicated that BoM negatively affected disease control rate (OR = 0.32, 95%CI: 0.13-0.82, P = 0.018), progression free survival (HR = 3.44, 95% CI:1.97-6.00, P < 0.001) and overall survival (HR = 3.24, 95% CI:1.62-6.50, P = 0.001), irrespective of programmed death-ligand 1 (PD-L1) expression. BoM patients were with significantly lower PD-L1, and this heterogeneity of TIME was then confirmed in the mIF staining, where 36 (61.0%) patients were clustered into immune-subtype A, with low expression of all the detected immune markers, similar to "cold" tumors, and 23 (39.0%) in cluster B with likely "hot" tumors. More patients in immune-subtype A were non-smokers (63.9% vs. 39.1% P = 0.063), with BoM (66.7% vs. 21.7%, P = 0.001), in stage IV(88.9% vs. 65.2%, P = 0.045), and with adenocarcinoma (91.7% vs. 69.6%, P = 0.037). Multivariate logistic regression indicated that BoM was independently associated with the "cold" immune characteristics (OR = 0.19, 95% CI:0.04-0.84, P = 0.028). Combination therapy with chemotherapy /antiangiogenesis or use of bisphosphonate during ICI treatment significantly improved clinical outcomes in BoM patients.BoM displays adverse impact on clinical outcomes after ICI treatments in NSCLC patients. The "cold" characteristics of TIME may be the underlying mechanism for the attenuated efficacy of ICIs in bone metastatic NSCLC patients.Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

基金：
This work was supported by the Science and Technology Planning Project of Guangdong Province [grant number 2017B030314166, 2020B1212030006].

基金编号： grant number 2017B030314166 2020B1212030006

语种：
外文
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中科院(CAS)分区：
出版当年[2021]版：
大类 | 2 区 医学
小类 | 2 区 肿瘤学 2 区 呼吸系统
最新[2025]版：
大类 | 2 区 医学
小类 | 3 区 肿瘤学 3 区 呼吸系统
JCR分区：
出版当年[2020]版：
Q1 RESPIRATORY SYSTEM Q2 ONCOLOGY
最新[2023]版：
Q1 ONCOLOGY Q1 RESPIRATORY SYSTEM

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China [2]Department of Oncology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China [3]Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China [4]Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China [2]Department of Oncology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China [3]Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China [4]Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China [*1]NO. 111, Dade Road, Guangzhou, Guangdong 510120, China.
推荐引用方式(GB/T 7714)：
Zhu Yan-Juan,Chang Xue-Song,Zhou Rui,et al.Bone metastasis attenuates efficacy of immune checkpoint inhibitors and displays cold immune characteristics in Non-small cell lung cancer[J].LUNG CANCER.2022,166:189-196.doi:10.1016/j.lungcan.2022.03.006.
APA：
Zhu Yan-Juan,Chang Xue-Song,Zhou Rui,Chen Ya-Dong,Ma Hao-Chuan...&Zhang Hai-Bo.(2022).Bone metastasis attenuates efficacy of immune checkpoint inhibitors and displays cold immune characteristics in Non-small cell lung cancer.LUNG CANCER,166,
MLA：
Zhu Yan-Juan,et al."Bone metastasis attenuates efficacy of immune checkpoint inhibitors and displays cold immune characteristics in Non-small cell lung cancer".LUNG CANCER 166.(2022):189-196

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