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Article ; Online: Immunomodulatory effect of locoregional therapy in the tumor microenvironment.

Xie, Lin / Meng, Zhiqiang

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 31, Issue 4, Page(s) 951–969

Abstract: Cancer immunotherapy appears to be a promising treatment option; however, only a subset of patients with cancer responds favorably to treatment. Locoregional therapy initiates a local antitumor immune response by disrupting immunosuppressive components, ... ...

Abstract	Cancer immunotherapy appears to be a promising treatment option; however, only a subset of patients with cancer responds favorably to treatment. Locoregional therapy initiates a local antitumor immune response by disrupting immunosuppressive components, releasing immunostimulatory damage-associated molecular patterns, recruiting immune effectors, and remodeling the tumor microenvironment. Many studies have shown that locoregional therapy can produce specific antitumor immunity alone; nevertheless, the effect is relatively weak and transient. Furthermore, increasing research efforts have explored the potential synergy between locoregional therapy and immunotherapy to enhance the long-term systemic antitumor immune effect and improve survival. Therefore, further research is needed into the immunomodulatory effects of locoregional therapy and immunotherapy to augment antitumor effects. This review article summarizes the key components of the tumor microenvironment, discusses the immunomodulatory role of locoregional therapy in the tumor microenvironment, and emphasizes the therapeutic potential of locoregional therapy in combination with immune checkpoint inhibitors.
MeSH term(s)	Humans ; Tumor Microenvironment ; Neoplasms/pathology ; Immunotherapy ; Immunity
Language	English
Publishing date	2023-01-24
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.01.017
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Article ; Online: Non-Hermitian topology in static mechanical metamaterials.

Wang, Aoxi / Meng, Zhiqiang / Chen, Chang Qing

Science advances

2023 Volume 9, Issue 27, Page(s) eadf7299

Abstract: The combination of broken Hermiticity and band topology in physical systems unveils a novel bound state dubbed as the non-Hermitian skin effect (NHSE). Active control that breaks reciprocity is usually used to achieve NHSE, and gain and loss in energy ... ...

Abstract	The combination of broken Hermiticity and band topology in physical systems unveils a novel bound state dubbed as the non-Hermitian skin effect (NHSE). Active control that breaks reciprocity is usually used to achieve NHSE, and gain and loss in energy are inevitably involved. Here, we demonstrate non-Hermitian topology in a mechanical metamaterial system by exploring its static deformation. Nonreciprocity is introduced via passive modulation of the lattice configuration without resorting to active control and energy gain/loss. Intriguing physics such as the reciprocal and higher-order skin effects can be tailored in the passive system. Our study provides an easy-to-implement platform for the exploration of non-Hermitian and nonreciprocal phenomena beyond conventional wave dynamics.
Language	English
Publishing date	2023-07-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adf7299
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Article ; Online: Case Report: Overcoming challenges in pancreatic cancer with liver metastases: a personalized therapeutic odyssey of TACE, ablation, and immunotherapy.

Zhu, Ying / Ning, Zhouyu / Meng, Zhiqiang

Frontiers in immunology

2023 Volume 14, Page(s) 1275782

Abstract: Pancreatic cancer represents a malignant neoplasm originating from pancreatic cells. The optimal approach to cancer treatment remains uncertain, lacking a definitive consensus. Here, we present a compelling case of a 49-year-old female with pancreatic ... ...

Abstract	Pancreatic cancer represents a malignant neoplasm originating from pancreatic cells. The optimal approach to cancer treatment remains uncertain, lacking a definitive consensus. Here, we present a compelling case of a 49-year-old female with pancreatic head cancer with liver metastases, as identified by CT and confirmed by biopsy. PET-CT indicated widespread metastatic involvement. TACE therapy with gemcitabine and cisplatin was initiated, yielding a stable disease response. The patient's high PD-L1 expression prompted TACE-PD-1 monoclonal antibody combination therapy. Subsequent treatments, including ablation, sustained PD-1 immunotherapy, and consolidation TACE, culminated in a complete response, as evidenced by imaging and tumor marker dynamics. Our case underscores the potential of multifaceted strategies in managing aggressive pancreatic cancer.
MeSH term(s)	Female ; Humans ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Programmed Cell Death 1 Receptor ; Chemoembolization, Therapeutic/methods ; Liver Neoplasms/secondary ; Pancreatic Neoplasms/therapy ; Pancreatic Neoplasms/pathology ; Immunotherapy ; Pancreatic Neoplasms
Chemical Substances	Programmed Cell Death 1 Receptor
Language	English
Publishing date	2023-10-11
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1275782
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Article ; Online: SDF-1α promotes subchondral bone sclerosis and aggravates osteoarthritis by regulating the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

Meng, Zhiqiang / Xin, Lujun / Fan, Bosheng

BMC musculoskeletal disorders

2023 Volume 24, Issue 1, Page(s) 275

Abstract: Background: Subchondral bone sclerosis is a major feature of osteoarthritis (OA), and bone marrow mesenchymal stem cells (BMSCs) are presumed to play an important role in subchondral bone sclerosis. Accumulating evidence has shown that stromal cell- ... ...

Abstract	Background: Subchondral bone sclerosis is a major feature of osteoarthritis (OA), and bone marrow mesenchymal stem cells (BMSCs) are presumed to play an important role in subchondral bone sclerosis. Accumulating evidence has shown that stromal cell-derived factor-1α (SDF-1α) plays a key role in bone metabolism-related diseases, but its role in OA pathogenesis remains largely unknown. The purpose of this study was to explore the role of SDF-1α expressed on BMSCs in subchondral bone sclerosis in an OA model. Methods: In the present study, C57BL/6J mice were divided into the following three groups: the sham control, destabilization of the medial meniscus (DMM), and AMD3100-treated DMM (DMM + AMD3100) groups. The mice were sacrificed after 2 or 8 weeks, and samples were collected for histological and immunohistochemical analyses. OA severity was assessed by performing hematoxylin and eosin (HE) and safranin O-fast green staining. SDF-1α expression in the OA model was measured using an enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (q-PCR), and immunohistochemistry. Micro-CT was used to observe changes in subchondral bone in the OA model. CD44, CD90, RUNX2, and OCN expression in subchondral bone were measured using q-PCR and immunohistochemistry. In vitro, BMSCs were transfected with a recombinant lentivirus expressing SDF-1α, an empty vector (EV), or siRNA-SDF-1α. Western blot analysis, q-PCR, and immunofluorescence staining were used to confirm the successful transfection of BMSCs. The effect of SDF-1α on BMSC proliferation was evaluated by performing a CCK-8 assay and cell cycle analysis. The effect of SDF-1α on the osteogenic differentiation of BMSCs was assessed by performing alkaline phosphatase (ALP) and alizarin red S (ARS) staining. Cyclin D1, RUNX2 and OCN expression were measured using Western blot analysis, q-PCR, and immunofluorescence staining. Results: SDF-1α expression in the DMM-induced OA model increased. In the DMM + AMD3100 group, subchondral bone sclerosis was alleviated, OA was effectively relieved, and CD44, CD90, RUNX2, and OCN expression in subchondral bone was decreased. In vitro, high levels of SDF-1α promoted BMSC proliferation and increased osteogenic differentiation. Cyclin D1, RUNX2, and OCN expression increased. Conclusion: The results of this study reveal a new molecular mechanism underlying the pathogenesis of OA. The targeted regulation of SDF-1α may be clinically effective in suppressing OA progression.
MeSH term(s)	Mice ; Animals ; Osteogenesis ; Chemokine CXCL12/metabolism ; Chemokine CXCL12/pharmacology ; Core Binding Factor Alpha 1 Subunit/metabolism ; Core Binding Factor Alpha 1 Subunit/pharmacology ; Cyclin D1/metabolism ; Sclerosis/metabolism ; Mice, Inbred C57BL ; Osteoarthritis/metabolism ; Mesenchymal Stem Cells/metabolism ; Cell Differentiation ; Cell Proliferation ; Bone Marrow Cells/metabolism ; Cells, Cultured
Chemical Substances	plerixafor (S915P5499N) ; Chemokine CXCL12 ; Core Binding Factor Alpha 1 Subunit ; Cyclin D1 (136601-57-5)
Language	English
Publishing date	2023-04-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2041355-5
ISSN	1471-2474 ; 1471-2474
ISSN (online)	1471-2474
ISSN	1471-2474
DOI	10.1186/s12891-023-06366-1
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Article: Editorial: Anti-cancer effects of botanical drugs targeting the tumor microenvironment.

Cheng, Chien-Shan / Wang, Ning / Meng, Zhiqiang

Frontiers in pharmacology

2023 Volume 14, Page(s) 1268094

Language	English
Publishing date	2023-08-17
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1268094
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Article ; Online: Long-lasting complete response to SHR-1701 plus famitinib in refractory advanced gallbladder cancer: A case report.

Yi, Lixia / Zhu, Xiaoyan / Xie, Jing / Meng, Zhiqiang

Human vaccines & immunotherapeutics

2023 Volume 19, Issue 3, Page(s) 2294575

Abstract: Biliary tract cancer (BTC) is an aggressive malignancy with few options for advanced-stage treatment. The combination of PD-1/PD-L1 inhibitors with famitinib, a receptor tyrosine kinase (RTK) inhibitor, has demonstrated improved clinical outcomes in ... ...

Abstract	Biliary tract cancer (BTC) is an aggressive malignancy with few options for advanced-stage treatment. The combination of PD-1/PD-L1 inhibitors with famitinib, a receptor tyrosine kinase (RTK) inhibitor, has demonstrated improved clinical outcomes in several clinical trials. We herein reported a case of a gallbladder cancer (GBC) patient with liver metastases, previously resistant to traditional chemotherapy. Remarkably, the patient achieved a complete response (CR) with a long-lasting survival benefit exceeding 3 years. This was achieved using a novel regimen combining SHR-1701, an anti-PD-L1/TGF-βR fusion protein, and famitinib, even though the patient had proficient mismatch repair (pMMR) and tested negative for PD-L1. Adverse events were limited and manageable. This is the first report of such a treatment regimen being applied in a clinical setting, suggesting that the SHR-1701 and famitinib combination may be a promising immunotherapeutic approach for patients with refractory advanced GBC.
MeSH term(s)	Humans ; Gallbladder Neoplasms/drug therapy ; Indoles ; Pyrroles ; Immune Checkpoint Inhibitors ; Pathologic Complete Response
Chemical Substances	famitinib (768FW21J3L) ; SHR-1701 ; Indoles ; Pyrroles ; Immune Checkpoint Inhibitors
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.1080/21645515.2023.2294575
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Article ; Online: Robotic Materials Transformable Between Elasticity and Plasticity.

Wang, Xinyuan / Meng, Zhiqiang / Chen, Chang Qing

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

2023 Volume 10, Issue 13, Page(s) e2206637

Abstract: Robotic materials, with coupled sensing, actuation, computation, and communication, have attracted increasing attention because they are able to not only tune their conventional passive mechanical property via geometrical transformation or material phase ...

Abstract	Robotic materials, with coupled sensing, actuation, computation, and communication, have attracted increasing attention because they are able to not only tune their conventional passive mechanical property via geometrical transformation or material phase change but also become adaptive and even intelligent to suit varying environments. However, the mechanical behavior of most robotic materials is either reversible (elastic) or irreversible (plastic), but not transformable between them. Here, a robotic material whose behavior is transformable between elastic and plastic is developed, based upon an extended neutrally stable tensegrity structure. The transformation does not depend on conventional phase transition and is fast. By integrating with sensors, the elasticity-plasticity transformable (EPT) material is able to self-sense deformation and decides whether to undergo transformation or not. This work expands the capability of the mechanical property modulation of robotic materials.
Language	English
Publishing date	2023-02-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2808093-2
ISSN	2198-3844 ; 2198-3844
ISSN (online)	2198-3844
ISSN	2198-3844
DOI	10.1002/advs.202206637
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Article ; Online: Insulin growth factor-1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β-catenin pathway.

Feng, Jing / Meng, Zhiqiang

Experimental and therapeutic medicine

2021 Volume 22, Issue 2, Page(s) 891

Abstract: Bone marrow mesenchymal stem cells (BMSCs) are stem cells that exist in bone marrow tissue and have osteogenic differentiation potential. Insulin growth factor-1 (IGF-1) plays a key role in the proliferation and osteogenic differentiation of BMSCs. ... ...

Abstract	Bone marrow mesenchymal stem cells (BMSCs) are stem cells that exist in bone marrow tissue and have osteogenic differentiation potential. Insulin growth factor-1 (IGF-1) plays a key role in the proliferation and osteogenic differentiation of BMSCs. However, the specific mechanism of IGF-1 in cell proliferation and osteogenic differentiation remains unclear. In the present study, BMSCs were transfected with lentivirus carrying the siRNA-Wnt3a gene, and the Wnt3a level in BMSCs was revealed to be reduced by western blotting, real-time quantitative polymerase chain reaction and immunofluorescence detection. Then, BMSCs were treated with 80 ng/ml IGF-1 in complete medium for 5 days. CCK-8 and cell cycle assays revealed that cell proliferation was significantly decreased in the siRNA-Wnt3a group than in the control group. The protein and mRNA levels of β-catenin and cyclin D1 were significantly downregulated in the siRNA-Wnt3a group compared with the control group. In addition, BMSCs were treated with IGF-1 in osteogenic differentiation medium for 7 and 21 days, and alkaline phosphatase staining and Alizarin Red staining demonstrated significantly reduced osteogenic differentiation ability in the siRNA-Wnt3a group compared with the control group. Furthermore, the protein and mRNA levels of β-catenin, RUNX2, and OPN were downregulated compared with the control group. Our findings revealed that IGF-1 promoted the proliferation and differentiation of BMSCs at least partially through the Wnt/β-catenin pathway. These findings provided new insight into the clinical treatment of bone disease.
Language	English
Publishing date	2021-06-17
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2683844-8
ISSN	1792-1015 ; 1792-0981
ISSN (online)	1792-1015
ISSN	1792-0981
DOI	10.3892/etm.2021.10323
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Article ; Online: Exploring the efficacy and safety of drug-eluting beads transarterial chemoembolization in pancreatic cancer liver metastasis.

Ning, Zhouyu / Zhu, Ying / Xie, Lin / Yan, Xia / Hua, Yongqiang / Meng, Zhiqiang

The British journal of radiology

2024 Volume 97, Issue 1157, Page(s) 1010–1015

Abstract: Objectives: Drug-eluting beads transarterial chemoembolization (DEB-TACE) has shown promise as a treatment modality for primary liver cancer and colorectal cancer liver metastasis. However, its role in pancreatic cancer liver metastasis (PCLM) remains ... ...

Abstract	Objectives: Drug-eluting beads transarterial chemoembolization (DEB-TACE) has shown promise as a treatment modality for primary liver cancer and colorectal cancer liver metastasis. However, its role in pancreatic cancer liver metastasis (PCLM) remains uncertain. This study aimed to investigate the efficacy and safety of DEB-TACE in PCLM patients. Methods: A retrospective study included 10 PCLM patients who underwent DEB-TACE using CalliSpheres® microspheres as the chemoembolization material. Treatment response, survival outcomes, adverse events, and liver function indexes were comprehensively assessed. Results: Among the patients, complete response, partial response, stable disease, and progressive disease rates were 0.0%, 40.0%, 30.0%, and 30.0%, respectively. The objective response rate was 40.0%, and the disease-control rate was 70.0%. The median progression-free survival (PFS) was 12.0 months (95% CI: 0.0-26.7), with a 1-year PFS rate of 48.0%. The median overall survival (OS) was 18.0 months (95% CI: 6.0-30.0), with a 1-year OS rate of 80.0%. Additionally, no significant differences were observed in any of the liver function indexes, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, etc., between pre- and posttreatment evaluations. Adverse events included pain, grade 1-2 vomiting, fever, and transient liver dysfunction. Conclusions: DEB-TACE demonstrates a promising treatment response, favorable survival profile, and satisfactory safety in PCLM patients. Advances in knowledge: This study adds to the current research by providing novel evidence on the efficacy, safety, and favorable survival outcomes of DEB-TACE in treating PCLM, highlighting its potential as an effective therapeutic option in this specific population.
MeSH term(s)	Humans ; Chemoembolization, Therapeutic/methods ; Male ; Liver Neoplasms/secondary ; Liver Neoplasms/therapy ; Female ; Retrospective Studies ; Middle Aged ; Pancreatic Neoplasms/therapy ; Pancreatic Neoplasms/pathology ; Aged ; Microspheres ; Treatment Outcome ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Adult
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2024-03-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2982-8
ISSN	1748-880X ; 0007-1285
ISSN (online)	1748-880X
ISSN	0007-1285
DOI	10.1093/bjr/tqae059
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Article ; Online: Single-cell transcriptome analysis revealed the immune profile of PD-1 blockade in gallbladder carcinoma liver metastasis.

Xie, Lin / Ning, Zhouyu / Hua, Yongqiang / Wang, Peng / Meng, Zhiqiang

Hepatology communications

2023 Volume 7, Issue 5

Abstract: Background: Gallbladder carcinoma is the most common cancer of the biliary tract, and the immune checkpoint blockade showed promising efficacy in the treatment of advanced gallbladder carcinoma. However, the underlying mechanisms remain unknown.: ... ...

Abstract	Background: Gallbladder carcinoma is the most common cancer of the biliary tract, and the immune checkpoint blockade showed promising efficacy in the treatment of advanced gallbladder carcinoma. However, the underlying mechanisms remain unknown. Methods: Single-cell RNA sequencing was used to reveal immune cell dynamics in an anti-PD-1 responder with gallbladder carcinoma liver metastases. Gene set variation analysis, pseudotime analysis, single-cell regulatory network inference and clustering analysis, and CellChat analysis were used to identify the functions of each cell cluster. Immunohistochemistry and multicolored immunohistochemistry analysis were applied to confirm the intratumoral cell types, and the prognostic value of CXCL13+CD8+T cells in patients with gallbladder carcinoma liver metastases with immunotherapy was evaluated. Four biliary tract carcinoma and 3 immunotherapy bulk RNA-seq datasets were analyzed to investigate the prognostic value of CXCL13+CD8+T cells and SPP1+TAMs. Result: A total of 19,648 high-quality single-cell transcriptome data were obtained from liver metastasis before and after aPD-1 therapy. We discovered improved cytotoxic activity in CD8+T cells and enhanced proinflammatory phenotypes in myeloid cells. The identified SPP1+TAMs were related to poor prognosis. The increased effector/memory T cells represented characteristics similar to exhausted T cells in transitory status after aPD-1therapy, which may play a crucial role in the antitumor immune response. We further revealed that CXCL13+T cells in a high subtype of biliary tract carcinoma were characterized as a 'hot tumor' profile with high immune scores, correlated to the immunostimulatory context with favorable survival, and can predict effective responses to immunotherapy. Conclusions: Our study provided an overview of immune cell dynamics in gallbladder carcinoma liver metastases after aPD-1 treatment and highlighted the importance of CXCL13+T cells in biliary tract carcinoma and effective responses to immunotherapy, which would advance the understanding and treatment of the disease.
MeSH term(s)	Humans ; Carcinoma/metabolism ; CD8-Positive T-Lymphocytes ; Gallbladder Neoplasms/drug therapy ; Gallbladder Neoplasms/genetics ; Gallbladder Neoplasms/metabolism ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Single-Cell Gene Expression Analysis ; Programmed Cell Death 1 Receptor/antagonists & inhibitors
Chemical Substances	Programmed Cell Death 1 Receptor
Language	English
Publishing date	2023-04-14
Publishing country	United States
Document type	Journal Article
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1097/HC9.0000000000000131
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