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Article: Immunotherapy for hepatobiliary malignancies: Progress and prospective.

Qin, Lun-Xiu

Hepatobiliary & pancreatic diseases international : HBPD INT

2022 Volume 21, Issue 5, Page(s) 409–412

MeSH term(s)	Carcinoma, Hepatocellular ; Humans ; Immunologic Factors ; Immunotherapy/adverse effects ; Liver Neoplasms/therapy ; Prospective Studies
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2022-09-07
Publishing country	Singapore
Document type	Editorial
ZDB-ID	2241386-8
ISSN	1499-3872
ISSN	1499-3872
DOI	10.1016/j.hbpd.2022.09.002
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Article: Expert consensus-promoting clinical excellence and ultimately benefitting patients.

Chen, Jin-Hong / Qin, Lun-Xiu

Hepatobiliary surgery and nutrition

2023 Volume 12, Issue 5, Page(s) 743–745

Language	English
Publishing date	2023-09-14
Publishing country	China (Republic : 1949- )
Document type	Editorial
ZDB-ID	2812398-0
ISSN	2304-389X ; 2304-3881
ISSN (online)	2304-389X
ISSN	2304-3881
DOI	10.21037/hbsn-23-435
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Article: Strategies for improving the efficacy of immunotherapy in hepatocellular carcinoma.

Zhu, Ying / Qin, Lun-Xiu

Hepatobiliary & pancreatic diseases international : HBPD INT

2022 Volume 21, Issue 5, Page(s) 420–429

Abstract: Primary liver cancer, mainly hepatocellular carcinoma (HCC), is the sixth most diagnosed cancer and third leading cause of cancer-related death globally. Recently, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in ... ...

Abstract	Primary liver cancer, mainly hepatocellular carcinoma (HCC), is the sixth most diagnosed cancer and third leading cause of cancer-related death globally. Recently, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. However, anti-PD-1 therapy with pembrolizumab or nivolumab as a single agent did not meet their predefined end points of overall survival in the KEYNOTE-240 and CheckMate 459 trials. It is urgent to understand the immunological rationale and explore novel ways to improve the efficacy of immunotherapy. The combination of ICIs with other therapies, such as tyrosine kinase inhibitors (TKIs), monoclonal antibodies, or local therapy, has been demonstrated to improve overall response rate and survival. In addition, modulating tumor microenvironment is a potential way to overcome the primary and secondary resistance to immunotherapies. In this review, we summarized the latest findings in the immune microenvironment, the mechanisms of their synergistic effects when combined with anti-VEGF agents or TKIs, as well as other kinds of immune treatment.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/pathology ; Humans ; Immune Checkpoint Inhibitors/adverse effects ; Immunologic Factors/therapeutic use ; Immunotherapy/adverse effects ; Liver Neoplasms/drug therapy ; Liver Neoplasms/pathology ; Nivolumab/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Tumor Microenvironment
Chemical Substances	Antibodies, Monoclonal ; Immune Checkpoint Inhibitors ; Immunologic Factors ; Protein Kinase Inhibitors ; Nivolumab (31YO63LBSN)
Language	English
Publishing date	2022-08-08
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2241386-8
ISSN	1499-3872
ISSN	1499-3872
DOI	10.1016/j.hbpd.2022.08.003
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Article: Biomarkers for response to immunotherapy in hepatobiliary malignancies.

Lin, Zhi-Fei / Qin, Lun-Xiu / Chen, Jin-Hong

Hepatobiliary & pancreatic diseases international : HBPD INT

2022 Volume 21, Issue 5, Page(s) 413–419

Abstract: Background: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic options of hepatobiliary malignancies. However, the clinical benefit provided by immunotherapy seems limited to a small subgroup of patients with ... ...

Abstract	Background: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic options of hepatobiliary malignancies. However, the clinical benefit provided by immunotherapy seems limited to a small subgroup of patients with hepatobiliary malignancies. The identification of reliable predictors of the response to immunotherapy is urgently needed. Data sources: Literature search was conducted in PubMed for relevant articles published up to May 2022. Information of clinical trials was obtained from https://clinicaltrials.gov/. Results: Biomarkers for ICI response of hepatobiliary malignancies remain in the exploration stage and lack compelling evidence. Tumor programmed death-ligand 1 (PD-L1) expression is the most widely studied biomarker in hepatocellular carcinoma (HCC) and biliary tract cancers (BTCs), but there are conflicting results on its predictive potential. Tumor mutational burden (TMB) is generally low both in HCC and BTCs, and the clinical trials of TMB are rare in hepatobiliary malignancies. Promisingly, mismatch repair deficiency (dMMR)/high microsatellite instability (MSI-H) may be a predictive biomarker of response to anti-PD-1 therapy in BTCs. Furthermore, some emerging biomarkers, such as gut microbiota, show predictive potential in the preliminary studies. Radiomics and liquid-biopsy biomarkers, including circulating tumor cells, circulating tumor DNA (ctDNA) and exosomal PD-L1 provide a quick and non-invasive approach for monitoring the ICI response, showing a new promising direction. Conclusions: Multiple potential biomarkers for predicting ICI response of hepatobiliary malignancies have been explored and tried to apply in clinic. Yet there is no robust evidence to prove their clinical value in predicting immunotherapeutic response for patients with hepatobiliary malignancies. The identification of predictors for response to ICIs is an urgent need and major challenge. Further studies are warranted to validate the role of emerging biomarkers in predicting immunotherapeutic responses.
MeSH term(s)	B7-H1 Antigen ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Humans ; Immune Checkpoint Inhibitors/adverse effects ; Immunotherapy/methods ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics
Chemical Substances	B7-H1 Antigen ; Biomarkers, Tumor ; Immune Checkpoint Inhibitors
Language	English
Publishing date	2022-08-08
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2241386-8
ISSN	1499-3872
ISSN	1499-3872
DOI	10.1016/j.hbpd.2022.08.002
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Article: Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges.

Yang, Xin / Lu, Lu / Zhu, Wen-Wei / Tao, Yi-Feng / Shen, Cong-Huan / Chen, Jin-Hong / Wang, Zheng-Xin / Qin, Lun-Xiu

Hepatobiliary & pancreatic diseases international : HBPD INT

2023 Volume 23, Issue 2, Page(s) 117–122

Abstract: Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava and ...

Abstract	Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic patients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.
MeSH term(s)	Humans ; Hepatectomy/adverse effects ; Liver Neoplasms/surgery ; Liver Transplantation/adverse effects ; Consensus
Language	English
Publishing date	2023-10-20
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2241386-8
ISSN	1499-3872
ISSN	1499-3872
DOI	10.1016/j.hbpd.2023.10.007
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Article ; Online: Pan-Cancer Analysis Reveals a Distinct Neutrophil Extracellular Trap-Associated Regulatory Pattern.

Shen, Xiao-Tian / Xie, Sun-Zhe / Xu, Jing / Yang, Lu-Yu / Qin, Lun-Xiu

Frontiers in immunology

2022 Volume 13, Page(s) 798022

Abstract: Background: Neutrophils form extracellular net-like structures called neutrophil extracellular traps (NETs). Emerging evidence has shown that cancer can induce NET formation; however, it is not fully understood how NETs influence cancer biology, and no ... ...

Abstract	Background: Neutrophils form extracellular net-like structures called neutrophil extracellular traps (NETs). Emerging evidence has shown that cancer can induce NET formation; however, it is not fully understood how NETs influence cancer biology, and no consensus has been reached on their pro- or antitumor effects. A comprehensive analysis of the global NET-associated gene regulatory network is currently unavailable and is urgently needed. Methods: We systematically explored and discussed NET enrichment, NET-associated gene regulatory patterns, and the prognostic implications of NETs in approximately 8,000 patients across 22 major human cancer types. We identified NET-associated regulatory gene sets that we then screened for NET-associated regulatory patterns that might affect patient survival. We functionally annotated the NET-associated regulatory patterns to compare the biological differences between NET-related survival subgroups. Results: A gene set variation analysis (GSVA) based on 23 major component genes was used to calculate a metric called the NET score. We found that the NET score was closely associated with many important cancer hallmarks, particularly inflammatory responses and epithelial-to-mesenchymal transition (EMT)-induced metastasis. Higher NET scores were related to poor immunotherapy response. Survival analysis revealed that NETs had diverse prognostic impacts among various cancer types. The NET-associated regulatory patterns linked to shorter or longer cancer patient survival were distinct from each other. Functional analysis revealed that more of the NET-associated regulatory genes linked to poor cancer survival were associated with extracellular matrix (ECM) remodeling and pan-cancerous risk factors. SPP1 was found to be highly expressed and correlated with NET formation in cancers with poor survival. We also found that the co-upregulation of NET formation and SPP1 expression was closely linked to increased EMT and poor survival, that SPP1 influenced NET-induced malignant capacity, and that SPP1 overproduction induced a robust formation of metastatic-promoting NETs. Conclusion: NETs were common across cancers but displayed a diverse regulatory pattern and outcome readouts in different cancer types. SPP1 is potentially the key to NET-related poor outcomes.
MeSH term(s)	Extracellular Traps/metabolism ; Humans ; Immunotherapy ; Neoplasms/pathology ; Neutrophils/metabolism ; Prognosis
Language	English
Publishing date	2022-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.798022
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Article ; Online: Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis.

Fu, Yan / Shen, Keyu / Wang, Hao / Wang, Shun / Wang, Xufeng / Zhu, Le / Zheng, Yan / Zou, Tiantian / Ci, Hongfei / Dong, Qiongzhu / Qin, Lun-Xiu

Signal transduction and targeted therapy

2024 Volume 9, Issue 1, Page(s) 63

Abstract: Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a "neural addiction" property and build up local nerve networks to achieve an enhanced ... ...

Abstract	Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a "neural addiction" property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis. Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment. However, whether intrahepatic cholangiocarcinoma (ICC) could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown. Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that ICC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes ICC metastasis by inducing epithelial-mesenchymal transition (EMT). Acetylcholine promoted ICC metastasis through interacting with its receptor, alpha 5 nicotine acetylcholine receptor subunits (CHRNA5). Furthermore, acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca
MeSH term(s)	Humans ; beta Catenin/metabolism ; Brain-Derived Neurotrophic Factor/genetics ; Nicotine ; Acetylcholine ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics ; Gemcitabine ; Glycogen Synthase Kinase 3 beta ; Cell Line, Tumor ; Cholangiocarcinoma/drug therapy ; Cholangiocarcinoma/genetics ; Bile Ducts, Intrahepatic/metabolism ; Bile Ducts, Intrahepatic/pathology ; Bile Duct Neoplasms/drug therapy ; Bile Duct Neoplasms/genetics ; Bile Duct Neoplasms/metabolism ; Neurotransmitter Agents ; Receptors, Cholinergic ; Tumor Microenvironment ; Benzenesulfonamides ; Benzylamines
Chemical Substances	beta Catenin ; Brain-Derived Neurotrophic Factor ; Nicotine (6M3C89ZY6R) ; KN 93 (139298-40-1) ; Acetylcholine (N9YNS0M02X) ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17) ; Gemcitabine ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Neurotransmitter Agents ; Receptors, Cholinergic ; Benzenesulfonamides ; Benzylamines
Language	English
Publishing date	2024-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2886872-9
ISSN	2059-3635 ; 2095-9907
ISSN (online)	2059-3635
ISSN	2095-9907
DOI	10.1038/s41392-024-01761-z
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Article ; Online: Inflammatory immune responses in tumor microenvironment and metastasis of hepatocellular carcinoma.

Qin, Lun-Xiu

Cancer microenvironment : official journal of the International Cancer Microenvironment Society

2012 Volume 5, Issue 3, Page(s) 203–209

Abstract: Metastasis is a multistage process that requires cancer cells to escape from the primary tumor, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of ...

Abstract	Metastasis is a multistage process that requires cancer cells to escape from the primary tumor, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumor microenvironment. There are growing evidences that tumors are sustained and promoted by inflammatory signals from the surrounding microenvironment. This review describes experimental data demonstrating the role of the inflammatory immune responses of microenvironment in metastases of hepatocellular carcinoma (HCC), points out the prospective areas for future research and possible new therapeutic approaches to control the metastasis of HCC.
Language	English
Publishing date	2012-06-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2422345-1
ISSN	1875-2284 ; 1875-2292
ISSN (online)	1875-2284
ISSN	1875-2292
DOI	10.1007/s12307-012-0111-1
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Article: [Osteopontin: a prognostic indicator for metastatic recurrence of hepatocellular carcinoma and a promising therapeutic target].

Qin, Lun-xiu

Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology

2011 Volume 19, Issue 4, Page(s) 247–248

MeSH term(s)	Carcinoma, Hepatocellular/pathology ; Humans ; Liver Neoplasms/pathology ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Osteopontin ; Prognosis
Chemical Substances	Osteopontin (106441-73-0)
Language	Chinese
Publishing date	2011-04
Publishing country	China
Document type	Journal Article
ISSN	1007-3418
ISSN	1007-3418
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Article ; Online: A Prognostic Nomogram for Hepatocellular Carcinoma Based on Wound Healing and Immune Checkpoint Genes.

Hu, Beiyuan / Shen, Xiaotian / Qin, Wei / Zhang, Lan / Zou, Tiantian / Dong, Qiongzhu / Qin, Lun-Xiu

Journal of clinical and translational hepatology

2022 Volume 10, Issue 5, Page(s) 891–900

Abstract: Background and aims: Wound healing and tumor progression share some common biological features; however, how variations in wound healing patterns affect hepatocellular carcinoma (HCC) prognosis remains unclear.: Methods: We analyzed the wound healing ...

Abstract	Background and aims: Wound healing and tumor progression share some common biological features; however, how variations in wound healing patterns affect hepatocellular carcinoma (HCC) prognosis remains unclear. Methods: We analyzed the wound healing patterns of 594 HCC samples from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) and correlated them with immune infiltration and the expression levels of immune checkpoint genes. A risk score, which we named the "heal.immune" score, was established via stepwise Cox estimation. We constructed a nomogram based on age, sex, TNM stage, and heal.immune score and explored its predictive value for HCC prognosis. Seventy-four clinical patients were enrolled in this study, and all were from Huashan Hospital of Fudan University between 2015 and 2017 to serve as an independent validation group. Results: We identified two distinct wound healing patterns in HCC. The biological processes of healing cluster 1 (C1) are related to metabolism, while those of healing cluster 2 (C2) are related to the inflammatory response and immune cell accumulation. A total of 565 wound healing-related genes (based on Gene Ontology) and 25 immune checkpoint genes were considered. By analyzing differentially expressed genes and implementing a stepwise Cox estimation analysis, six genes with Conclusions: We established a prognostic nomogram based on the heal.immune gene signature, which includes six wound healing- and immunity-related genes. This nomogram accurately predicts the OS of HCC patients.
Language	English
Publishing date	2022-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019822-7
ISSN	2310-8819 ; 2225-0719
ISSN (online)	2310-8819
ISSN	2225-0719
DOI	10.14218/JCTH.2021.00296
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