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World Journal of Gastrointestinal Surgery 2021年第10期13卷 1136-1148页

作者： Lin-Lin Zheng Chang-Cheng Tao Zong-Gui Tao Kai Zhang An-Ke Wu Jian-Xiong Wu Wei-Qi Rong Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Imaging Jinan City People's HospitalShandong First Medical UniversityJinan 271199Shandong ProvinceChina

In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and *** is considered to be an effective treatment for advanced *** checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced ***,treating advanced HCC is still a great challenge,and the need for new treatments remains *** review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.

关键词： programmed cell death 1/programmed cell death ligand 1 inhibitors Targeted therapy Hepatocellular carcinoma programmed cell death 1 programmed cell death ligand 1

programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma

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World Journal of Clinical Oncology 2024年第7期15卷 859-866页

作者： Shi-Qiong Zhou Peng Wan Sen Zhang Yuan Ren Hong-Tao Li Qing-Hua Ke Department of Chemoradiotherapy The First Affiliated Hospital of Yangtze UniversityJingzhou 434000Hubei ProvinceChina

BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor *** advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in *** article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for *** Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer *** the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent *** April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control *** Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation *** patients completed the scheduled course of chemoradiotherapy in the control *** on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 pa

关键词： Immunotherapy Concurrent chemoradiotherapy Locally advanced pancreatic adenocarcinoma programmed cell death 1 Sintilimab

Transarterial chemoembolization combined with lenvatinib and sintilimab vs lenvatinib alone in intermediate-advanced hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 52-61页

作者： Fei-Da Wu Hai-Feng Zhou Wei Yang Di Zhu Bi-Fei Wu Hai-Bin Shi Sheng Liu Wei-Zhong Zhou Department of Interventional Radiology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is the most common form of liver cancer that has limited treatment options and a poor *** chemoembolization(TACE)is the first-line treatment for intermediate-stage HCC but can induce tumour hypoxia,thereby promoting *** studies suggested that combining TACE with anti-angiogenic therapies and immunotherapy might im-prove ***,a tyrosine kinase inhibitor,has demonstrated superior outcomes compared to sorafenib,while immune checkpoint inhibitors such as sintilimab show potential when combined with ***,the efficacy and safety of TACE combined with lenvatinib and sintilimab(TACE+SL)compared to TACE with lenvatinib alone(TACE+L)in patients with intermediate-ad-vanced HCC has not yet been *** To evaluate the efficacy and safety of TACE+SL therapy in comparison to TACE+L therapy in patients with intermediate-advanced *** A retrospective analysis was performed on patients with intermediate-advanced HCC who received TACE plus lenvatinib with or without sintilimab between September 2019 and September *** characteristics were compared,and propensity score matching was *** survival(OS),progression-free survival(PFS),and objective response rate(ORR)were evaluated between the two groups,and adverse events were *** The study included 57 patients,with 30 in the TACE+SL group and 27 in the TACE+L *** TACE+SL group demonstrated significantly improved median PFS and OS compared to the TACE+L group(PFS:14.1 months vs 9.6 months,P=0.016;OS:22.4 months vs 14.1 months,P=0.039),along with a higher ORR(70.0%vs 55.6%).After propensity score matching,30 patients were included,with the TACE+SL group again showing longer median PFS and a trend toward improved OS(PFS:14.6 months vs 9.2 months,P=0.012;OS:23.9 months vs 16.3 months,P=0.063),and a higher ORR(73.3%vs 53.3%).No severe adverse events were *** TACE+SL demonstrat

关键词： Hepatocellular carcinoma Transarterial chemoembolization Sintilimab Lenvatinib Immunotherapy programmed cell death 1 Prognosis

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

PD-1 Involvement in Peripheral Blood CD8+T Lymphocyte Dysfunction in Patients with Acute-on-chronic Liver Failure

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 283-290页

作者： Xiaoshuang Zhou Yidong Li Yaqiu Ji Tian Liu Ninghui Zhao Jiefeng He Jia Yao Department of Nephrology Shanxi Provincial People’s HospitalShanxi Medical UniversityTaiyuanShanxiChina Department of Gastroenterology Shanxi Bethune HospitalShanxi Medical UniversityTaiyuanShanxiChina Department of Hepatobiliary Surgery Shanxi Bethune HospitalShanxi Medical UniversityTaiyuanShanxiChina Institute of Liver Disease and Organ Transplantation Shanxi Medical UniversityTaiyuanShanxiChina

Background and Aims:programmed cell death-1(PD-1)plays an important role in downregulating T lymphocytes but the mechanisms are still poorly *** study aimed to explore the role of PD-1 in CD8^(+)T lymphocyte dysfunction in hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).Methods:Thirty patients with HBV-ACLF and 30 healthy controls(HCs)were *** differences in the numbers and functions of CD8^(+)T lymphocytes,PD-1 and glucose transporter-1(Glut1)expression from the peripheral blood of patients with HBV-ACLF and HCs were *** vitro,the CD8^(+)T lymphocytes from HCs were cultured(HC group)and the CD8^(+)T lymphocytes from ACLF patients were cultured with PD-L1-IgG(ACLF+PD-1 group)or IgG(ACLF group).The numbers and functions of CD8^(+)T lymphocytes,PD-1 expression,glycogen uptake capacity,and Glut1,hexokinase-2(HK2),and pyruvate kinase(PKM2)expression were analyzed among the HC group,ACLF group and ACLF+***:The absolute numbers of CD8^(+)T lymphocytes in the peripheral blood from patients with HBVACLF were lower than in the HCs(p<0.001).The expression of PD-1 in peripheral blood CD8^(+)T lymphocytes was lower in HCs than in patients with HBV-ACLF(p=0.021).Compared with HCs,PD-1 expression was increased(p=0.021)and Glut1 expression was decreased(p=0.016)in CD8^(+)T lymphocytes from the HBV-ACLF *** vitro,glycogen uptake and functions of ACLF CD8^(+)T lymphocytes were significantly lower than that in HCs(p=0.017;all p<0.001).When PD-1/PD-L1 was activated,the glycogen uptake rate and expression levels of Glut1,HK2,and PKM2 showed a decreasing trend(ACLF+PD-1 group compared to ACLF group,all p<0.05).The functions of CD8^(+)T lymphocytes in the ACLF+PD-1 group[using biomarkers of Ki67,CD69,IL-2,interferon-gamma,and tumor necrosis factor-alpha-were lower than in the ACLF group(all p<0.05).Conclusions:CD8^(+)T lymphocyte dysfunction is observed in patients with ***-1-induced T lymphocyte dysfunction mig

关键词： Acute and chronic liver failure programmed cell death 1 Immune function Glycolysis Glut1

Stereotactic body radiotherapy combined with sintilimab in patients with recurrent or oligometastatic hepatocellular carcinoma: A phase Ⅱ clinical trial

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World Journal of Gastroenterology 2023年第24期29卷 3871-3882页

作者： Yi-Xing Chen Ping Yang Shi-Suo Du Yuan Zhuang Cheng Huang Yong Hu Wen-Chao Zhu Yi-Yi Yu Tian-Shu Liu Zhao-Chong Zeng Department of Radiation Oncology Zhongshan HospitalFudan UniversityShanghai 200032China Liver Cancer Institute Zhongshan HospitalFudan UniversityShanghai 200032China Department of Medical Oncology Zhongshan HospitalFudan UniversityShanghai 200032China

BACKGROUND Stereotactic body radiotherapy(SBRT)and programmed cell death 1 inhibitors have shown potential in treating hepatocellular carcinoma(HCC)in retrospective *** To evaluate the efficacy of combining SBRT with sintilimab for patients with recurrent or oligometastatic *** This trial involved patients with recurrent or oligometastatic HCC intravenously treated with SBRT plus sintilimab every 3 wk for 12 mo or until disease *** primary endpoint was progression-free survival(PFS).RESULTS Twenty-five patients were enrolled from August 14,2019,to August 23,*** median treatment duration was 10.2(range,0.7-14.6)*** was delivered at a median dose of 54(range,48-60)Gy in 6(range,6-10)*** median follow-up time was 21.9(range,10.3-39.7)mo,and 32 targeted lesions among 25 patients were evaluated for treatment response according to the Response Evaluation Criteria in Solid Tumors version *** median PFS was 19.7 mo[95%confidence interval(CI):16.9-NA],with PFS rates of 68%(95%CI:52-89)and 45.3%(95%CI:28-73.4)at 12 and 24 mo,*** median overall survival(OS)was not reached,with OS rates of 91.5%(95%CI:80.8-100.0)and 83.2%(95%CI:66.5-100.0)at 12 and 24 mo,*** 1-and 2-year local control rate were 100%and 90.9%(95%CI:75.4%-100.0%),*** confirmed objective response rate and disease control rate was 96%,and 96%,*** adverse events were graded as 1 or 2,and grade 3 adverse events were observed in three *** SBRT plus sintilimab is an effective,well-tolerated treatment regimen for patients with recurrent or oligometastatic HCC.

关键词： Stereotactic body radiotherapy programmed cell death 1 Sintilimab Hepatocellular carcinoma Efficacy and safety

Immune signature of small bowel adenocarcinoma and the role of tumor microenvironment

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World Journal of Gastroenterology 2024年第8期30卷 794-798页

作者： Grigorios Christodoulidis Marina Nektaria Kouliou Konstantinos Eleftherios Koumarelas Department of General Surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such *** detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor *** involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor *** are linked to genetic disorders and risk factors,including chronic inflammatory *** unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable *** cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic *** instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to *** presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI *** tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.

关键词： programmed cell death 1 programmed cell death-ligand 1 programmed death ligand Small bowel adenocarcinoma Tumor infiltrating lymphocytes Tumor microenvironment Microsatellite instability

Landscape of transarterial chemoembolization represented interventional therapy for hepatocellular carcinoma

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World Journal of Gastrointestinal Surgery 2024年第12期16卷 3903-3906页

作者： Yang-Yang Fu Wen-Mao Li Hong-Qiao Cai Yan Jiao Department of The First Operation Room The First Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Department of Rehabilitation The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Department of Hepatobiliary and Pancreatic Surgery General Surgery CenterThe First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

This article discusses the article written by Tan et *** chemoembol-ization(TACE)is one of the main treatment methods for advanced hepatocellular carcinoma(HCC).There are other vascular interventional therapies,including drug-eluting bead TACE,transarterial radioembolization,and hepatic arterial infusion *** combined with anti-angiogenesis therapy may improve tumor control and prolong progression free *** combination therapy of TACE and immunotherapy may improve the clinical efficacy of *** future research,more basic and clinical studies are needed to explore the immunogenic intervention therapy.

关键词： Transarterial chemoembolization Interventional therapy Hepatocellular carcinoma Anti-angiogenesis Immunotherapy programmed cell death 1

PD1/PDL1 expression is associated with increased TIM3 expression and tumor-infiltrating T lymphocytes in fibroblastic sarcoma

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PD1/PDL1 expression is associated with increased TIM3 expres...

Relationship between PD-1/PD-L1 pathway and MLH1,MSH2 expression in cervical cancer and its clinical significance in Xinjiang Uygur Autonomous Region, China

第十四届全国免疫学学术大会

作者： Huoying Chen Hongbo Liu Jie Ai Shengjun Xiao Department of Laboratory Medicine The Second Affiliated Hospital of Guilin Medical University Department of Pathology The Second Affiliated Hospital of Guilin Medical University

Background:Immunotherapy based on blocking immune checkpoints that activates the anti-tumor immune response can be an addition to the treatment regimen of soft tissue *** combined therapy of inhibiting T cell immunoglobulin domain and mucin domain 3(TIM3) and programmed cell death 1/programmed death-ligand 1(PD1/PDL1) has been shown encouraging therapeutic effects in some solid ***,expression of PD1/PDL1 and TIM3 in fibroblastic sarcomas is ill defined,which limits the application of these immune checkpoint inhibitors in such type of ***:To delineate the expression of PD1/PDL1 and TIM3,as well as their relationship with tumor-infiltrating T lymphocytes(TILs) in fibroblastic sarcomas,hoping to provide a clue on whether such tumors may benefit from immune checkpoint inhibitors ***:The expression pattern of PD1,PDL1 and TIM3,as well as the accumulation of TILs in 68 tissue microarray cores of fibroblastic sarcomas were determined by immunostaining and then statistically ***:Both PD1 and PDL1 expression was only observed in 10.27% of fibroblastic sarcomas,whereas TIM3 was expressed in almost all ***,only the positive expression of PDL1 is related to tumors with high grade and staging.A considerable number of TILs,including CD4,CD8 A-positive T cells,and a small group of FoxP3-positive T cells,were also observed in most *** density of TIM3 is positively correlated with that of ***,higher density of TIM3,CD4,CD8 A and FoxP3 was observed in PD1 and PDL1 double-positive fibroblastic ***:TILs with high expression of TIM3 may constitute the immunosuppression of fibroblastic sarcomas;patients with fibroblastic sarcomas with high expression of PD1/PDL1 and TIM3 may benefit from combination therapy of PD1/PDL1 and TIM3 inhibitors.

关键词： fibroblastic sarcoma programmed cell death 1 programmed death-ligand 1 T cell immunoglobulin domain and mucin domain 3 tumor-infiltrating T lymphocytes

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Relationship between PD-1/PD-L1 pathway and MLH1,MSH2 expres...