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N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA

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National Science Review 2024年第3期11卷 72-91页

作者： Jiawang Zhou Haisheng Zhang Ke Zhong Lijun Tao Yu Lin Guoyou Xie Yonghuang Tan You Wu Yunqing Lu Zhuojia Chen Jiexin Li Xin Deng Qin Peng Zigang Li Hongsheng Wang Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat-sen University Sun Yat-sen University Cancer center State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine Department of Biomedical Sciences City University of Hong Kong Institute of Systems and Physical Biology Shenzhen Bay Laboratory

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer（CRC） cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione（GSH） via the upregulation of RRM2B——a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3 UTR of RRM2B increased its m RNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence（CDS） of OPA1——an essential GTPase protein for mitochondrial inner membrane fusion——also increased m RNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.

关键词： m6A mitochondrial fusion glutathione OPA1 colorectal cancer

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Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

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oncology Research 2024年第8期32卷 1309-1322页

作者： ANA S.CVETANOVIC MATTEO LAMBERTINI KEVIN PUNIE GORANA G.MATOVINA BRKO NIKOLA D.ZIVKOVIC MAJA J.POPOVIC MARIJANA M.MILOVIC KOVACEVIC LAZAR S.POPOVIC Department for oncology Medical Faculty NisUniversity of NisNis18000Serbia Clinic of oncology University Clinical Centre NisNis18000Serbia Department of Internal Medicine and Medical Sciences(DiMI) School of MedicineUniversity of GenovaGenova16100Italy Department of Medical oncology U.O.C Clinica di Oncologia MedicaIRCCS Ospedale Policlinico San MartinoGenova16100Italy Department of General Medical oncology and Multidisciplinary breast Centre Leuven Cancer InstituteUniversity Hospitals LeuvenLeuven3001Belgium Department of Medical oncology Oncology Institute of VojvodinaSremska Kamenica21208Serbia Department for Pathology Medical Faculty NisUniversity of NisNis18000Serbia center for Pathology University Clinical Centre NisNis18000Serbia Faculty of Medicine University of Novi SadNovi Sad21000Serbia Department of Medical oncology Institute of Oncology and Radiology SerbiaBelgrade11000Serbia

Oncofertility is an extremely signiﬁcant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but signiﬁcantly contributes to preserving life *** effect of chemotherapy can range from minimal effects to complete ovarian *** data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and *** ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufﬁciency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian ***,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological ***,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor *** addition,studies on hematological malignancies have yielded negative results;nevertheless,theﬁndings must be interpreted with caution owing to numerous *** guidelines from the American Society of Clinical oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not *** this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisﬁeld

关键词： Gonadotropin-releasing hormone agonists(GnRHa) Fertility preservation Premature ovarian insufficiency(POI) Premenopausal patients

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Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 686-699页

作者： Junfen XU Mengyan TU Department of Gynecologic oncology Women’s HospitalZhejiang University School of MedicineHangzhou 310006China Zhejiang Provincial Clinical Research center for Obstetrics and Gynecology Hangzhou 310006China

Objective:The present study used single-cell RNA sequencing(scRNA-seq)to characterize the cellular composition of ovarian carcinosarcoma(OCS)and identify its molecular ***:scRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor *** staining was used for *** scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma(HGSOC)tumors and other OCS ***:Both malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this *** identified four epithelial cell subclusters with different biological *** them,epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog(BRCA1)and DNA topoisomerase 2-α(TOP2A)expression and was related to drug resistance and cell *** analyzed the interaction between epithelial and mesenchymal cells and found that fibroblast growth factor(FGF)and pleiotrophin(PTN)signalings were the main pathways contributing to communication between these ***,we compared the malignant epithelial and mesenchymal cells of this OCS tumor with our previous published HGSOC scRNA-seq data and OCS *** the epithelial subclusters in the OCS tumor could be found in the HGSOC ***,the mesenchymal subcluster C14 exhibited specific expression patterns in the OCS tumor,characterized by elevated expression of cytochrome P450 family 24 subfamily A member 1(CYP24A1),collagen type XXIIIα1 chain(COL23A1),cholecystokinin(CCK),bone morphogenetic protein 7(BMP7),PTN,Wnt inhibitory factor 1(WIF1),and insulin-like growth factor 2(IGF2).Moreover,this subcluster showed distinct characteristics when compared with both another previously published OCS tumor and normal ovarian ***:This study provides the single-cell transcriptomics signature of human OCS,which constitutes a new resource for elucidating OCS diversity.

关键词： Ovarian carcinosarcoma Single-cell RNA sequencing(scRNA-seq) Tumor heterogeneity

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Identification of prognostic molecular subtypes and model based on CD8+ T cells for lung adenocarcinoma

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BIOCELL 2024年第3期48卷 473-490页

作者： HONGMIN CAO YING XUE FEI WANG GUANGYAO LI YULAN ZHEN JINGWEN GUO Internal Medicine-oncology Dongguan Songshan Lake Central HospitalDongguan523326China Tumor center First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan523888China

Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer *** the speciﬁc functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of ***:Gens related to CD8+T cells were identiﬁed by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal *** gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T *** of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were veriﬁed by cell ***:This study deﬁned two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being signiﬁcantly associated with the prognosis of *** heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 signiﬁcant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD ***,the model also showed general applicability in external validation ***-risk patients could beneﬁt more from taking immunotherapy and were signiﬁcantly related to the resistance to anticancer *** results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was signiﬁcantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD *** of CD200R1 greatly increased the invasiveness of the LUAD cell

关键词： CD8+T cell Lung adenocarcinoma Molecular subtype Prognostic model Immunotherapy

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Small nucleolar RNA and its potential role in the oncogenesis and development of colorectal cancer

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World Journal of Gastroenterology 2024年第2期30卷 115-127页

作者： Yang-Zheng Lan Zheng Wu Wen-Jia Chen Ze-Xuan Fang Xin-Ning Yu Hua-Tao Wu Jing Liu The breast center Cancer Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Department of General Surgery The First Affiliated Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina

Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein *** have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human *** is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in *** the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer *** research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous ***,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of ***,current comprehension of the potential roles of snoRNAs in CRC remains *** review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.

关键词： Small nucleolar RNAs Colorectal cancer Dysregulation Biomarker

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Phase Ib study of anti-EGFR antibody(SCT200)in combination with anti-PD-1 antibody(SCT-I10A)for patients with RAS/BRAF wild-type metastatic colorectal cancer

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Cancer Biology & Medicine 2024年第7期21卷 636-650页

作者： Ming Bai Yao Lu Chunmei Shi Jianwei Yang Wei Li Xianli Yin Chenghui Huang Lin Shen Liangzhi Xie Yi Ba Department of GI Medical oncology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin Key Laboratory of Digestive CancerTianjin 300060China Fujian Medical University Union Hospital Fuzhou 350001China Fujian Provincial Cancer Hospital Fuzhou 350014China Cancer center The First Hospital of Jilin UniversityChangchun 130021China Department of Medical oncology Gastroenterology and Urology Hunan Cancer HospitalAffiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Department of oncology The Third Xiangya HospitalCentral South UniversityChangsha 410013China Department of Gastrointestinal oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Bejing)Peking University Cancer Hospital and InstituteBeijing 100142China Beijing Engineering Research center of Protein and Antibody Sinocelltech Ltd.Bejing 100176China Department of Cancer center Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100010China

Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical *** with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and *** primary endpoints were the objective response rate(ORR)and *** secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,*** ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,*** treatment-related adverse events(TRAEs)were ***,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination ***:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety *** head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration ***04229537).

关键词： Colorectal cancer SCT-I10A SCT200 epidermal growth factor receptor programmed cell death 1

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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:Massachusetts Institute of Technology BostonMA 02139USA Present address:Melvin and Bren Simon Comprehensive Cancer center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

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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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Nursing Care and Causative Analysis of Grade IV Capsular Contracture Following breast Cancer Expander Implantation

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Advances in breast Cancer Research 2024年第1期13卷 1-9页

作者： Rong Chen Nan Zhang Huiting Zhang State Key Laboratory of oncology in South China Collaborative Innovation Center for Cancer Medicine Department of Breast Cancer Sun Yat-sen University Cancer Hospital Guangzhou China

Objective: By observing the treatment and nursing care of a patient with Grade IV capsular contracture following breast cancer expander implantation and subsequent Stage II reconstruction, we aim to analyze the reasons for the formation of capsular contracture after Stage I expander implantation and prevent its recurrence following Stage II reconstruction. Methods: In May 2020, the patient noticed an increase in the size of a breast mass. In August, she underwent AC-THP neoadjuvant chemotherapy, followed by a “right breast-conserving nipple-areolar subglandular excision + right axillary lymph node dissection + expander implantation” surgery in November 2020. Radiation therapy began in January 2021. During radiation therapy, the patient experienced severe breast hardening, distortion, tenderness, and was diagnosed with Grade IV capsular contracture. To relieve the capsular contracture, the patient underwent a “contracted capsule incision and release procedure + removal of the right breast expander + right breast implantation” surgery in July 2021. Postoperatively, measures were taken to prevent incision infection, emphasizing aseptic techniques, ensuring smooth negative pressure drainage, reducing skin flap tension, monitoring skin flap blood supply, actively preventing subcutaneous effusion and hematoma, and applying appropriate compression dressings. Results: The patient was discharged after the removal of the drainage tube. During the postoperative follow-up at 3 and 6 months, there was no recurrence of capsular contracture, and the breast appeared full, upright, and relatively soft. There were no complications such as hematoma, infection, breast implant rupture, breast sagging, or displacement. The patient had a good outcome without additional financial or surgical burdens. Conclusion: The occurrence of Grade IV capsular contracture in the patient is generally related to infection after Stage I expander implantation, improper compression dressing, excessive salin

关键词： breast Cancer Capsular Contracture Expander Implantation

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Penpulimab,an anti-PD-1 antibody,for heavily pretreated metastatic nasopharyngeal carcinoma:a single-arm phase II study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3056-3062页

作者： Xiaozhong Chen Wei Wang Qingfeng Zou Xiaodong Zhu Qin Lin Yi Jiang Yan Sun Liangfang Shen Lin Wang Guorong Zou Xiaoyan Lin Shaojun Lin Minying Li Ying Wang Ruilian Xu Rui Ao Rensheng Wang Haifeng Lin Shuang Huang Tingting Xu Wenting Li Mengying Xia Yu Xia Zhongmin Wang Baiyong Li Jingao Li Chaosu Hu Department of Radiation oncology Cancer Hospital of the University of ChineseAcademy of Sciences(Zhejiang Cancer Hospital)HangzhouChina Gastroenterology and Urology Department II Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina Clinical Research center for Gastrointestinal Cancer in Hunan Province ChangshaChina Department of Medical oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouChina Department of Radiation oncology Guangxi Medical University Affiliated Tumor Hospital&Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)Ministry of Education&Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency TumorGuangxi Medical UniversityNanningChina Department of Radiation oncology Cancer CenterThe First Affiliated Hospital of Xiamen UniversityXiamenChina Department of Medical oncology Cancer Hospital of Shantou University Medical CollegeShantouChina Department of Radiation oncology Peking University Cancer Hospital&InstituteBeijingChina Department of oncology Xiangya Hospital Central South UniversityChangshaChina Department of Medical oncology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouChina Department of oncology The Affiliated Panyu Central Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Medical oncology Fujian Medical University Union HospitalFuzhouChina Department of Radiation oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina Department of Radiation Therapy for Thoracic Tumors Zhongshan City People’s HospitalZhongshanChina Tumor Radiotherapy center Chongqing University Cancer HospitalChongqing Cancer HospitalChongqing Cancer InstituteChongqingChina Department of oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSo

Penpulimab is an anti-programmed cell death-1(PD-1)IgG1 antibody with no Fc gamma receptor(FcγR)binding activity,and thus theoretically reduced immune-related adverse events(irAEs)while maintaining *** single-arm,phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma(NPC)who had failed two or more lines of previous systemic *** received 200-mg penpulimab intravenously every 2 weeks(4 weeks per cycle)until disease progression or intolerable *** primary endpoint was objective response rate(ORR)per RECIST(version 1.1),as assessed by an independent radiological review *** secondary endpoints included progression-free survival(PFS)and overall survival(OS).One hundred thirty patients were enrolled and 125 were efficacy *** the data cutoff date(September 28,2022),1 patient achieved complete response and 34 patients attained partial *** ORR was 28.0%(95%CI 20.3–36.7%).The response was durable,with 66.8%still in response at 9 ***-three patients(26.4%)were still on *** median PFS and OS were 3.6 months(95%CI=1.9–7.3 months)and 22.8 months(95%CI=17.1 months to not reached),***(7.6%)patients experienced grade 3 or higher *** has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients,supporting further clinical development as third-line treatment of metastatic NPC.

关键词： metastatic nasopharyngeal supporting

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