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Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

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International Journal of Oral Science 2024年第1期16卷 110-121页

作者： Zheqi Liu Zhen Zhang Yu Zhang Wenkai Zhou Xu Zhang Canbang Peng Tong Ji Xin Zou Zhiyuan Zhang Zhenhu Ren Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghaiChina Department of Oral and Maxillofacial Surgery Zhongshan HospitalFudan UniversityShanghaiChina School and hospital of Stomatology Kunming Medical UniversityKunmingChina center for Tumor Diagnosis&Therapy Jinshan HospitalFudan UniversityShanghaiChina Department of Pathology Jinshan HospitalFudan UniversityShanghaiChina Hainan Western Central hospital Academician Zhang Zhiyuan Team Innovation CenterDanzhouChina

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

关键词： CXCL12 microenvironment squamous

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Integrated bulk and single-cell transcriptome data identify clinically relevant cell populations in clear cell renal cell carcinoma

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Genes & Diseases 2024年第1期11卷 42-45页

作者： Pingbao Zhang Pu Zhang Jun Gao Xiaosong Li Chengcheng Wei Weihui Liu QingLiu He Yuan Zhang Department of Urology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Urology Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghai 200032China Clinical Molecular Medicine Testing center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouFujian 362000China Department of Nephrology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China

Renal cell carcinoma,which consists of three main histological subtypes,namely,clear cell renal cell carcinoma(ccRCC),papillary RCC(pRCC),and chromophobe RCC(chRCC),accounts for most kidney cancer cases.ccRCC accounts for approximately 85%of all RcC cases,1 and it is a malignant tumor with multiple molecular features and a poor prognosis.Studies have shown that ccRCC is one of the most immune and vaso-invasive cancer types.2 Considering that ccRCC is not sensitive to either radiotherapy or chemotherapy,targeted therapies.

关键词： chemotherapy cancer cases

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Ischemia-reperfusion injury:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 558-596页

作者： Meng Zhang Qian Liu Hui Meng Hongxia Duan Xin Liu Jian Wu Fei Gao Shijun Wang Rubin Tan Jinxiang Yuan The Collaborative Innovation center Jining Medical UniversityJiningShandong 272067China Clinical medical college Jining Medical UniversityJiningShandong 272067China Second Clinical medical college Jining Medical UniversityJiningShandong 272067China shanghai Institute of Cardiovascular Diseases Zhongshan Hospital and Institutes of Biomedical SciencesFudan UniversityShanghaiChina Institute of Zoology Chinese Academy of SciencesBeijingChina Department of Physiology Basic medical schoolXuzhou Medical UniversityXuzhou 221004China

Ischemia-reperfusion(I/R)injury paradoxically occurs during reperfusion following ischemia,exacerbating the initial tissue damage.The limited understanding of the intricate mechanisms underlying I/R injury hinders the development of effective therapeutic interventions.The Wnt signaling pathway exhibits extensive crosstalk with various other pathways,forming a network system of signaling pathways involved in I/R injury.This review article elucidates the underlying mechanisms involved in Wnt signaling,as well as the complex interplay between Wnt and other pathways,including Notch,phosphatidylinositol 3-kinase/protein kinase B,transforming growth factor-β,nuclear factor kappa,bone morphogenetic protein,N-methyl-D-aspartic acid receptor-Ca2+-Activin A,Hippo-Yes-associated protein,toll-like receptor 4/toll-interleukine-1 receptor domain-containing adapter-inducing interferon-β,and hepatocyte growth factor/mesenchymal-epithelial transition factor.In particular,we delve into their respective contributions to key pathological processes,including apoptosis,the inflammatory response,oxidative stress,extracellular matrix remodeling,angiogenesis,cell hypertrophy,fibrosis,ferroptosis,neurogenesis,and blood-brain barrier damage during I/R injury.Our comprehensive analysis of the mechanisms involved in Wnt signaling during I/R reveals that activation of the canonical Wnt pathway promotes organ recovery,while activation of the non-canonical Wnt pathways exacerbates injury.Moreover,we explore novel therapeutic approaches based on these mechanistic findings,incorporating evidence from animal experiments,current standards,and clinical trials.The objective of this review is to provide deeper insights into the roles of Wnt and its crosstalk signaling pathways in I/R-mediated processes and organ dysfunction,to facilitate the development of innovative therapeutic agents for I/R injury.

关键词： therapeutic reperfusion damage

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NF-κB in biology and targeted therapy:new insights and translational implications

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1322-1358页

作者： Qing Guo Yizi Jin Xinyu Chen Xiaomin Ye Xin Shen Mingxi Lin Cheng Zeng Teng Zhou Jian Zhang Department of medical Oncology Fudan University Shanghai Cancer CenterNo.270Dong'an RoadShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina State Key Laboratory of Oncogenes and Related Genes Renj-Med-X Stem Cell Research CenterShanghai Cancer Institute&Department of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127PR China Department of Cardiology the First Affiliated Hospital of Sun Yat-Sen University58 Zhongshan 2nd RoadGuangzhou 510080China Department of Neurology Rujin HospitalShanghai JiaoTong University Schoolof MedicineShanghaiChina

NF-κB signaling has been discovered for nearly 40 years.Initially,NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses.However,with extensive and in-depth investigations,researchers have discovered that its role can be expanded to a variety of signaling mechanisms,biological processes,human diseases,and treatment options.In this review,we first scrutinize the research process of NF-κB signaling,and summarize the composition,activation,and regulatory mechanism of NF-κB signaling.We investigate the interaction of NF-κB signaling with other important pathways,including PI3K/AKT,MAPK,JAK-STAT,TGF-β,Wnt,Notch,Hedgehog,and TLR signaling.The physiological and pathological states of NF-κB signaling,as well as its intricate involvement in inflammation,immune regulation,and tumor microenvironment,are also explicated.Additionally,we illustrate how NF-κB signaling is involved in a variety of human diseases,including cancers,inflammatory and autoimmune diseases,cardiovascular diseases,metabolic diseases,neurological diseases,and covID-19.Further,we discuss the therapeutic approaches targeting NF-κB signaling,including IKK inhibitors,monoclonal antibodies,proteasome inhibitors,nuclear translocation inhibitors,DNA binding inhibitors,TKls,non-coding RNAs,immunotherapy,and CAR-T.Finally,we provide an outlook for research in the field of NF-κB signaling.We hope to present a stereoscopic,comprehensive NF-κB signaling that will inform future research and clinical practice.

关键词： PI3K/AKT diseases involvement

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Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer

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Genes & Diseases 2024年第3期11卷 338-350页

作者： Xin Xu Yuan Fang Somaira Nowsheen Ye-Xiong Li Zhenkun Lou Min Deng State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China Department of General Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Department of Dermatology University of California San DiegoSan DiegoCA 92093USA Department of Oncology Mayo ClinicRochesterMN 55905USA

The adenosine monophosphate(AMP)-activated protein kinase(AMPK)sits at a cen-tral node in the regulation of energy metabolism and tumor progression.AMPK is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy stores.Previous studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic cancer.In this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)stiffness.We found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM stiffness.This regulation of AMPK requires the Hippo kinases but not LKB1/CaMKKp.Hippo kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM stiffness.Furthermore,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival outcome.The activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC growth.Together,these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness-Hippo kinases-AMPK signaling and low glucose-LKB1-AMPK signaling pathways as an effective therapeutic strategy against PDAC.

关键词： AMPKactivity Cellularmetabolic switch ECM stiffness Hippokinase signaling Pancreaticductal adenocarcinoma

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GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases

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The Innovation 2024年第2期5卷 27-41页

作者： Zheyan Fang Gang Zhao Shuang Zhao Xueting Yu Runyang Feng You-en Zhang Haomin Li Lei Huang Zhenyang Guo Zhentao Zhang Mukaddas Abdurahman Hangnan Hong Peng Li Bing Wu Jinhang Zhu Xin Zhong Dong Huang Hao Lu Xin Zhao Zhaoyang Chen Wenbin Zhang Junjie Guo Hongchao Zheng Yue He Shengying Qin Haojie Lu Yun Zhao Xiangdong Wang Junbo Ge Hua Li Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai 200032China Department of Cardiology Zhongshan HospitalFudan UniversityShanghai 200032China Department of medical Examination Shanghai Xuhui District Central HospitalShanghai 200031China Department of Cardiology and Institute of Clinical Medicine Renmin HospitalHubei University of MedicineShiyan 442000China Clinical Data center Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Molecular Celland Cancer BiologyUniversity of Massachusetts Chan Medical SchoolWorcesterMA 01605USA Bio-X Institute Key Laboratory for The Genetics of Developmental and Neuropsychiatric DisordersShanghai Jiao Tong UniversityShanghai 200030China Department of Cardiology Heart Center of Fujian ProvinceFujian Medical University Union HospitalFuzhou 350001China Department of Cardiology Sir Run Run Shaw Hospitalaffiliated with Zhejiang University School of MedicineHangzhou 310020China Department of Cardiology The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Cardiology Shanghai Xuhui District Central HospitalShanghai 200031China Department of Cardiology Shanghai Eighth People’s HospitalShanghai 200235China Department of Chemistry and Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China School of Life Science and technology Shanghai Tech University100 Haike RoadShanghai 201210China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Department of Pulmonary and Critical Care Medicine Zhongshan Hospital

Partial endothelial-to-mesenchymal transition(EndMT)is an intermediate phenotype observed in endothelial cells(ECs)undergoing a transition toward a mesenchymal state to support neovascularization during(patho)physiological angiogenesis.Here,we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4(GTF2H4)as a positive regulator of this process.In addition,we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3(ERCC3)to co-regulate partial EndMT.Furthermore,by using phosphorylation proteomics and site-directed mutagenesis,we demonstrated that GTF2H4 was involved in the phosphorylation of receptor coactivator 3(NCOA3)at serine 1330,which promoted the interaction between NCOA3 and p65,resulting in the transcriptional activation of NF-κB and the NF-kB/Snail signaling axis during partial EndMT.In vivo experiments confirmed that GTF2H4 significantly promoted partial EndMT and angiogenesis after ischemic injury.Collectively,our findings reveal that targeting GTF2H4 is promising for tissue repair and offers potential opportunities for treating hypoxic/ischemic diseases.

关键词： ischemic activation GTF

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Landscape of human organoids:Ideal model in clinics and research

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The Innovation 2024年第3期5卷 146-164页

作者： Xinxin Han Chunhui Cai Wei Deng Yanghua Shi Lanyang Li Chen Wang Jian Zhang Mingjie Rong Jiping Liu Bangjiang Fang Hua He Xiling Liu Chuxia Deng Xiao He Xin Cao Organ Regeneration X Lab Lisheng East China Institute of BiotechnologyPeking UniversityJiangsu 226200China shanghai Lisheng Biotech Shanghai 200092China LongHua hospital Shanghai University of Traditional Chinese Medicine725 Wanping South RoadXuhui DistrictShanghai 200032China Department of Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200125China Department of Neurosurgery Third Affiliated HospitalNaval Medical UniversityShanghai 200438China shanghai Key Laboratory of Forensic Medicine Shanghai Forensic Service PlatformAcademy of Forensic ScienceMinistry of JusticeShanghai 200063China Cancer center Faculty of Health SciencesUniversity of MacaoTaipaMacao SARChina Ministry of Education Frontiers Science center for Precision Oncology University of MacaoTaipaMacao SAR 999078China CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China zhongshan hospital Institute of Clinical Science Fudan University Shanghai Medical CollegeShanghai 200032China

In the last decade,organoid research has entered a golden era,signifying a pivotal shift in the biomedical landscape.The year 2023 marked a milestone with the publication of thousands of papers in this arena,reflecting exponential growth.However,amid this burgeoning expansion,a comprehensive and accurate overview of the field has been conspicuously absent.Our review is intended to bridge this gap,providing a panoramic view of the rapidly evolving organoid landscape.We meticulously analyze the organoid field from eight distinctive vantage points,harnessing our rich experience in academic research,industrial application,and clinical practice.We present a deep exploration of the advances in organoid technology,underpinned by our long-standing involvement in this arena.Our narrative traverses the historical genesis of organoids and their transformative impact across various biomedical sectors,including oncology,toxicology,and drug development.We delve into the synergy between organoids and avant-garde technologies such as synthetic biology and single-cell omics and discuss their pivotal role in tailoring personalized medicine,enhancing high-throughput drug screening,and constructing physiologically pertinent disease models.Our comprehensive analysis and reflective discourse provide a deep dive into the existing landscape and emerging trends in organoid technology.We spotlight technological innovations,methodological evolution,and the broadening spectrum of applications,emphasizing the revolutionary influence of organoids in personalized medicine,oncology,drug discovery,and other fields.Looking ahead,we cautiously anticipate future developments in the field of organoid research,especially its potential implications for personalized patient care,new avenues of drug discovery,and clinical research.We trust that our comprehensive review will be an asset for researchers,clinicians,and patients with keen interest in personalized medical strategies.We offer a broad view of the present and prospective capabilities of organoi

关键词： landscape intended advances

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Colorectal cancer’s burden attributable to a diet high in processed meat in the Belt and Road Initiative countries

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 182-196页

作者： Gu Liu Chang-Min Li Fei Xie Qi-Lai Li Liang-Yan Liao Wen-Jun Jiang Xiao-Pan Li Guan-Ming Lu Department of Gastrointestinal Surgery The First Affiliated HospitalJinan UniversityGuangzhou 510630Guangdong ProvinceChina Department of Gastrointestinal Surgery Chenzhou Third People’s HospitalChenzhou 423000Hunan ProvinceChina Department of Gastrointestinal Surgery Chenzhou First People’s Hospital and the First Affiliated Hospital of Xiangnan UniversityChenzhou423000 Hunan ProvinceChina Department of Breast and Thyroid Surgery the Affiliated Hospital of Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina Department of Health Management center Zhongshan HospitalShanghai Medical College of Fudan UniversityShanghai 200032China

BACKGROUND Colorectal cancer(CRC)plays a significant role in morbidity,mortality,and economic cost in the Belt and Road Initiative(“B and R”)countries.In addition,these countries have a substantial consumption of processed meat.However,the burden and trend of CRC in relation to the consumption of a diet high in processed meat(DHPM-CRC)in these“B and R”countries remain unknown.AIM To analyze the burden and trend of DHPM-CRC in the“B and R”countries from 1990 to 2019.METHODS We used the 2019 Global Burden of Disease Study to collate information regarding the burden of DHPM-CRC.Numbers and age-standardized rates(ASRs)of deaths along with the disability-adjusted life years(DALYs)were determined among the“B and R”countries in 1990 and 2019.Using joinpoint regression analysis,the average annual percent change(AAPC)was used to analyze the temporal trends of age-standardized DALYs rate(ASDALR)from 1990 to 2019 and in the final decade(2010–2019).RESULTS We found geographical differences in the burden of DHPM-CRC among“B and R”countries,with the three highest-ranking countries being the Russian Federation,China,and Ukraine in 1990,and China,the Russian Federation,and Poland in 2019.The burden of DHPM-CRC generally increased in most member countries from 1990 to 2019(all P<0.05).The absolute number of deaths and DALYs in DHPM-CRC were 3151.15[95%uncertainty interval(UI)665.74-5696.64]and 83249.31(95%UI 15628.64-151956.31)in China in 2019.However,the number of deaths(2627.57-2528.51)and DALYs(65867.39-55378.65)for DHPM-CRC in the Russian Federation has declined.The fastest increase in ASDALR for DHPM-CRC was observed in Vietnam,Southeast Asia,with an AAPC value of 3.90%[95%confidence interval(CI):3.63%-4.16%],whereas the fastest decline was observed in Kyrgyzstan,Central Asia,with an AAPC value of-2.05%(95%CI:-2.37%to-1.73%).A substantial upward trend in ASR of mortality,years lived with disability,years of life lost,and DALYs from DHPM-CRC changes in 1990-2019 and the final decade(2010-2019)for most Maritime Silk Route memb

关键词： Belt and Road Initiative countries Colorectal cancer Burden of disease Dietary risk factors Processed meat Disability-adjusted life years Trend analysis

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Bioinspired polysaccharide-based nanocomposite membranes with robust wet mechanical properties for guided bone regeneration

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National Science Review 2024年第3期11卷 215-226页

作者： Jian-Hong Xiao Zhen-Bang Zhang JiaHao Li Si-Ming Chen Huai-Ling Gao YinXiu Liao Lu Chen ZiShuo Wang YiFan Lu YuanZhen Hou HengAn Wu DuoHong Zou Shu-Hong Yu Department of Chemistry New Cornerstone Science Laboratory Institute of Biomimetic Materials&Chemistry Anhui Engineering Laboratory of Biomimetic MaterialsDivision of Nanomaterials&Chemistry Hefei National Research Center for Physical Sciences at the Microscale University of Science and Technology of China Department of Dental Implant center Stomatologic Hospital and College Key Laboratory of Oral Diseases Research of Anhui Province Anhui Medical University CAS Key Laboratory of Mechanical Behavior and Design of Materials Department of Modern Mechanics CAS Center for Excellence in Complex System Mechanics University of Science and Technology of China Department of Oral Surgery College of Stomatology National Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Institute of Innovative Materials(I2M) Department of Chemistry Department of Materials Science and Engineering Southern University of Science and Technology

Polysaccharide-based membranes with excellent mechanical properties are highly desired. However, severe mechanical deterioration under wet conditions limits their biomedical applications. Here, inspired by the structural heterogeneity of strong yet hydrated biological materials, we propose a strategy based on heterogeneous crosslink-and-hydration（HCH） of a molecule/nano dual-scale network to fabricate polysaccharide-based nanocomposites with robust wet mechanical properties. The heterogeneity lies in that the crosslink-and-hydration occurs in the molecule-network while the stress-bearing nanofiber-network remains unaffected. As one demonstration, a membrane assembled by bacterial cellulose nanofiber-network and Ca2+-crosslinked and hydrated sodium alginate molecule-network is designed. Studies show that the crosslinked-and-hydrated molecule-network restricts water invasion and boosts stress transfer of the nanofiber-network by serving as interfibrous bridge. Overall, the molecule-network makes the membrane hydrated and flexible; the nanofiber-network as stress-bearing component provides strength and toughness.The HCH dual-scale network featuring a cooperative effect stimulates the design of advanced biomaterials applied under wet conditions such as guided bone regeneration membranes.

关键词： bioinspiration heterogeneous crosslink-and-hydration dual-scale network nanocomposite membrane wet mechanical properties guided bone regeneration

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Association of previously irradiated stable brain metastases with outcomes of atezolizumab-treated non-small cell lung cancer: A pooled analysis of individual patient data from three randomized trials

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Cancer Communications 2024年第2期44卷 278-281页

作者： Tiantian Guo Yue Zhou Fei Liang Zezhou Wang Vincent Bourbonne Lukas Käsmann Nora Sundahl Abraham Jing-Ching Wu Jianjiao Ni Zhengfei Zhu Department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiP.R.China shanghai Clinical Research center for Radiation Oncology ShanghaiP.R.China shanghai Key Laboratory of Radiation Oncology ShanghaiP.R.China Department of Biostatistics Zhongshan HospitalFudan UniversityShanghaiP.R.China Department of Cancer Prevention Fudan University Shanghai Cancer CenterShanghaiP.R.China Radiation Oncology Department University HospitalBrestFrance Department of Radiation Oncology University HospitalLMU MunichMunichGermany Department of Radiation Oncology AZ GroeningeKortrijkBelgium Department of Radiation Oncology Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA Institute of Thoracic Oncology Fudan UniversityShanghaiP.R.China

Dear Editor:Brain metastasis(BM)has long been recognized as a prognostic factor associated with poor prognosis for non-small cell lung cancer(NSCLC)in the era of con-ventional chemotherapy and targeted therapy[1].In the era of immunotherapy,controversial findings have been reported regarding the prognostic significance of BM in patients with NSCLC treated with programmed death-1/programmed death-ligand 1(PD-1/PD-L1)inhibitors.

关键词： chemotherapy NSCLC metastasis death

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