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The correlation and overlaps between pd-l1 expression and classical genomic aberrations in Chinese lung adenocarcinoma patients: a single center case series

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Cancer Biology & Medicine 2019年第4期16卷 811-821页

作者： Jianghua Wu Wei Sun Haiyue Wang Xiaozheng Huang Xinyu Wang Weiyang Jiang ling Jia Ping Wang Qin Feng Dongmei lin Department of Pathology Peking University Cancer Hospital&InstituteKey Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Beijing 100142China Department of Pathology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center of CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China

Objective:To investigate the correlation and overlaps between pd-l1 expression and classical genomic aberrations in Chinese lung adenocarcinoma(lADC)***:We reviewed 428 consecutive,surgically resected cases of lADC from October 2015 to December 2016 from our ***-l1 expression was evaluated based on tumor proportion score(TPS).Correlation and co-occurrence of pd-l1 expression level with those of classical driver genes,such as EGFR,AlK,ROS-1,and KRAS and with clinical variables and disease-free survival(DFS)were ***:Seventy of the 428 cases(16.4%)showed TPS≥1%,and 21 cases(4.9%)showed TPS≥50%.pd-l1 positive expression was significantly associated with male gender,smoking,advanced TNM stage,and solid histologic *** TPS≥1% and ≥50%were correlated with the absence of an EGFR mutation(PlK rearrangement(P=0.024).KRAS mutation was associated with TPS≥50%(P=0.035).pd-l1 positivity commonly overlapped with the alterations of classical driver oncogenes(58.5%with TPS≥1% and 42.9% with TPS≥50%).Approximately three-quarters of pd-l1 positive cases co-occurred with classical therapeutic-gene aberrations in cases with stage III/IV cancer or cancer *** could be divided into four subgroups based on the expression profile of current routine biomarkers for potential therapeutic ***:pd-l1 expression is not only closely correlated with classic gene alterations but also commonly overlaps with the aberrations of classical driver oncogenes in Chinese lADC *** findings provide a useful overview of clinical strategies that rely on the profile of routinely used molecular biomarkers.

关键词： lung adenocarcinoma pd-l1 expression classical genomic aberrations molecular biomarkers

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pd-l1:expression regulation

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Blood Science 2023年第2期5卷 77-91页

作者： Yu-Jie Zhou Guoli li Jiyin Wang Mengyuan liu Zihan Wang Yu Song Xulong Zhang Xi Wang Department of Immunology School of Basic Medical SciencesCapital Medical UniversityBeijingChina National Center for Infectious Diseases Beijing Ditan HospitalCapital Medical UniversityBeijingChina Beijing Key laboratory of Emerging Infectious Diseases Beijing Ditan HospitalCapital Medical UniversityBeijingChina Beijing Institute of Infectious Diseases BeijingChina Department of Medical laboratory Beijing Tongren HospitalCapital Medical UniversityBeijingChina

Programmed death-ligand 1(pd-l1),expressed on the surface of tumor cells,can bind to programmed cell death-1(pd-1)on T *** interaction of pd-1 and pd-l1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their *** cancers express high levels of pd-l1 and exploit pd-l1/pd-1 signaling to evade T-cell immunity,and immunotherapies targeting the pd-1/pd-l1 axis have been shown to exert remarkable anti-tumor effects;however,not all tumor patients benefit from these ***,study of the mechanisms regulating pd-l1 expression are *** this review,we explore regulation of pd-l1 expression in the contexts of gene transcription,signaling pathways,histone modification and remodeling,microRNAs,long noncoding RNAs,and post-translational *** developments in studies of agents that block pd-l1 and correlations between immunotherapies targeting pd-1/pd-l1 and pd-l1 expression are also *** review will assist in understanding of pd-l1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy.

关键词： Drug discovery Epigenetics Immune checkpoint blockage Immunotherapy pd-l1 expression

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pd-l1表达指导的信迪利单抗与帕博利珠单抗联合或不联合含铂双药化疗治疗未经治晚期非小细胞肺癌患者:一项2期随机对照试验(CTONG1901)

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Science Bulletin 2024年第4期69卷 535-543页

作者：刘思阳黄婕邓嘉怡徐崇锐严红虹杨明意黎扬斯柯娥娥郑明英王震林嘉欣甘彬张绪超陈华军汪斌超涂海燕杨衿记钟文昭李扬秋周清吴一龙 Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhou 510632China Guangdong lung Cancer Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Chinese Thoracic Oncology Group(CTONG) Guangzhou 510055China Institute of Hematology School of MedicineKey Laboratory for Regenerative Medicine of Ministry of EducationJinan UniversityGuangzhou 510632China

No direct comparison has been performed between different programmed cell death-1(pd-1)inhibitors for first-line treatment in patients with advanced non-small cell lung cancer(NSClC).The feasibility of using pd-l1-expression-guided immunotherapy remains *** this open-label,phase 2 study(NCT04252365),patients with advanced NSClC without EGFR or AlK alterations were randomized(1:1)to receive sintilimab or pembrolizumab monotherapy(pd-l1 expression≥50%),or sintilimab or pembrolizumab plus platinum-based chemotherapy(pd-l1 expressionle size was calculated by optimal two-stage *** primary endpoint was the objective response rate(ORR).The study included 71 patients(sintilimab arms,n=35;pembrolizumab arms,n=36)and met its primary endpoint,with a confirmed ORR of 51.4%(18/35)in the sintilimab *** confirmed ORR(95%confidence interval)was 46.2%(19.2%,74.9%)and 42.9%(17.7%,71.1%)for patients treated with sintilimab and pembrolizumab monotherapy;and 54.5%(32.2%,75.6%)and 45.4%(24.4%,67.8%)for those treated with sintilimab-and pembrolizumab-based combination *** median progression-free survival was6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination *** median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination ***-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III ***,the incidence of rash was higher with sintilimab than pembrolizumab *** is the first prospective phase 2 study to directly compare two anti-pd-1 antibodies as first-line treatment in advanced *** was efficacious and well-tolera

关键词： pd-1 inhibitor Non-small cell lung cancer Pembrolizumab Sintilimab pd-l1 expression

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