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The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy

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Science China(Life Sciences) 2024年第8期67卷 1549-1562页

作者： Peidong Zhang Peiwei Li Muya Tang Ryan CGimple Liang Huang Jing Yue Qiuhong Shen Yiwei Du Qian Zhang Zhengnan Yang Haihuai He Kailin Yang Linjie Zhao Shengtao Zhou department of Obstetrics and Gynecology Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOEState Key Laboratory of BiotherapyWest China Second HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Physician Scientist Training Program Department of MedicineWashington University School of MedicineSt.Louis 63110USA department of Neurosurgery State Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China department of Radiation oncology Taussig Cancer CenterCleveland ClinicCleveland 44106USA

Mechanics shape cell and tissue plasticity and maintain their *** cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic ***,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains ***,we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas(TCGA)*** the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway *** subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical *** further found that the responses of two subtypes of cancers,one with the optimal outcome and the other with the worst prognosis,to a classical mechanotherapeutic agent(Fasudil,RhoA/ROCK inhibitor)were totally different,indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic ***,our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.

关键词： pan-cancer cancer mechanics multi-omics immunology

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Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li Qianfeng Zhang Zhiqian Li Long Ren Dayi Pan Qiyong Gong Zhongwei Gu Hao Cai Kui Luo department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging key laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China key laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STING *** with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

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Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 854-868页

作者： Yunzhu Lin Xiang Wang Shi He Zhongxin Duan Yunchu Zhang Xiaodong Sun Yuzhu Hu Yuanyuan Zhang Zhiyong Qian Xiang Gao Zhirong Zhang key laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China department of Pharmacy Evidence-based Pharmacy CenterWest China Second University HospitalKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenSichuan UniversityChengdu 610041China department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China department of Radiation oncology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengdu 610041China

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor(i PDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of p IL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation,macrophage polarization and DC maturation. The F-DPC/p IL-12/i PDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/p IL-12/i PDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

关键词： IL-12encodinggene Checkpointblocker Nanoparticles Targeted delivery Tumormicroenvironment Immune escape Ovarian cancer Immunotherapy

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Recent progresses of exosome-liposome fusions in drug delivery

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Chinese Chemical Letters 2024年第2期35卷 107-117页

作者： Lulu Zheng Bo Hu Deyao Zhao Wenjing Liu Qing Liu Yuanyu Huang Shaobo Ruan School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China department of Radiation oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Beijing key laboratory of Drug Resistance Tuberculosis Research Beijing Tuberculosis and Thoracic Tumor Research Instituteand Beijing Chest HospitalCapital Medical UniversityBeijing 101149China

Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all *** to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past ***,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide ***,the emerging exosome-liposome fusion strategy has become a potential approach to solve such ***,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease *** review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational *** current challenge and future perspective regarding their clinical translation and application will also be discussed.

关键词： Exosome Liposome Membrane fusion Drug delivery Disease treatment

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The role of cholesterol metabolism in lung cancer

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oncology Research 2024年第10期32卷 1613-1621页

作者： Xiu W. Liu X. Hu K. Zhang Q. Shi H. department of thoracic oncology and state key laboratory of biotherapy Cancer Center West China Hospital Sichuan University Chengdu 610041 China West China School of Medicine Sichuan University Chengdu 610041 China department of Postgraduate Students West China School of Medicine Chengdu 610041 China department of biotherapy Cancer Center West China Hospital Sichuan University Chengdu 610041 China

Elevated serum cholesterol metabolism is associated with a reduced risk of lung cancer. Disrupted cholesterol metabolism is evident in both lung cancer patients and tumor cells. Inhibiting tumor cell cholesterol uptake or biosynthesis pathways, through the modulation of receptors and enzymes such as liver X receptor and sterol-regulatory element binding protein 2, effectively restrains lung tumor growth. Similarly, promoting cholesterol excretion yields comparable effects. Cholesterol metabolites, including oxysterols and isoprenoids, play a crucial role in regulating cholesterol metabolism within tumor cells, consequently impacting cancer progression. In lung cancer patients, both the cholesterol levels in the tumor microenvironment and within tumor cells significantly influence cell growth, proliferation, and metastasis. The effects of cholesterol metabolism are further mediated by the reprogramming of immune cells such as T cells, B cells, macrophages, myeloid-derived suppressor cells, among others. Ongoing research is investigating drugs targeting cholesterol metabolism for clinical treatments. Statins, targeting the cholesterol biosynthesis pathway, are widely employed in lung cancer treatment, either as standalone agents or in combination with other drugs. Additionally, drugs focusing on cholesterol transportation have shown promise as effective therapies for lung cancer. In this review, we summarized current research regarding the rule of cholesterol metabolism and therapeutic advances in lung cancer. © 2024 The Authors.

关键词： Cholesterol metabolism Immune cells Lung cancer Targeted strategies

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Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International Cancer Institute Beijing 100191China Institute of Cancer Research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer *** mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting ***,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of *** analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based *** expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of ***16 binds to HBB and promotes HBB accumulation by inhibiting ***16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the ***,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in ***,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang department of thoracic Surgery and oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical department Genecast Biotechnology Co.LtdWuxiChina department of Radiation oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina department of thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina department of Medical oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

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World Journal of Gastrointestinal oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong department of Colorectal Cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely ***9,a key regulator of transcription,may influence the occurrence and progression of *** expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in *** normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor ***,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this *** To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and *** We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of *** also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma *** The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy *** analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal *** This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

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Development of small molecule drugs targeting immune checkpoints

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Cancer Biology & Medicine 2024年第5期21卷 382-399页

作者： Luoyi Chen Xinchen Zhao Xiaowei Liu Yujie Ouyang Chuan Xu Ying Shi department of oncology Sichuan Academy of Medical SciencesSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610054China Institute for Breast Health Medicine State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Acupuncture and Massage College Chengdu University of Traditional Chinese MedicineChengdu 611137China

Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune *** of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely ***,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule *** structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical *** way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic *** ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle *** this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.

关键词： Immune checkpoints small molecule drugs programmed death protein 1 CD47 signal-regulatory proteinα

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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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Signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： Si-Yang Liu Song Dong Xue-Ning Yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji Yang Qing Zhou Hong-Rui Li Ke Liu Wendy Wu Si-Yang Maggie Liu Wen-Zhao Zhong Yi-Long Wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina department of thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina department of thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian key laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry oncology Corporation FuzhouChina Chinese thoracic oncology Group(CTONG) GuangzhouChina department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

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