A5020076697- Immune Cell Function and Interaction
- Tryptophan and brain disorders
- Immunotherapy and Immune Responses
- interferon and immune responses
- Parasitic Infections and Diagnostics
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Stress Responses and Cortisol
- Heat shock proteins research
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- Cytokine Signaling Pathways and Interactions
- Influenza Virus Research Studies
- Cancer survivorship and care
- Respiratory viral infections research
- Inflammasome and immune disorders
- Veterinary medicine and infectious diseases
- thermodynamics and calorimetric analyses
- Coccidia and coccidiosis research
- Immune cells in cancer
- Spaceflight effects on biology
- Reproductive System and Pregnancy
- Extracellular vesicles in disease
Newcastle University
2017-2024
First People's Hospital of Kunshan
2024
The Fourth People's Hospital
2024
Jiangsu University
2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2022-2023
Augusta University
2009-2022
Georgia Regents Medical Center
2013-2022
China Pharmaceutical University
2022
Tianjin Medical University
2021
Yili Friendship Hospital
2021
Cytosolic DNA sensing is an important process during the innate immune response that activates stimulator of interferon genes (STING) adaptor and induces IFN-I. STING incites spontaneous immunity immunogenic tumor growth accordingly, agonists induce regression therapy-resistant tumors. However DNA, agonists, apoptotic cells can also promote tolerogenic responses via by activating immunoregulatory mechanisms such as indoleamine 2,3 dioxygenase (IDO). Here, we show IDO activity induced in...
Cancer-secreted exosomal miRNAs are emerging mediators of cancer-stromal cross-talk in the tumor environment. Our previous array cervical squamous cell carcinoma (CSCC) clinical specimens identified upregulation miR-221-3p. Here, we show that miR-221-3p is closely correlated with peritumoral lymphangiogenesis and lymph node (LN) metastasis CSCC. More importantly, characteristically enriched transferred by CSCC-secreted exosomes into human lymphatic endothelial cells (HLECs) to promote HLECs...
Abstract CD73, an ecto-5′-nucleotidase (NT5E), serves as immune checkpoint by generating adenosine (ADO), which suppresses activation through the A 2A receptor. Elevated CD73 levels in tumor tissues correlate with poor clinical outcomes. However, crucial source of activity within microenvironment remains unspecified. Here, we demonstrate that cancer-associated fibroblasts (CAFs) constitute prominent hi population human colorectal cancers (CRCs) and two − murine models, including a modified...
Abstract The nasal epithelium is a plausible entry point for SARS-CoV-2, site of pathogenesis and transmission, may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical outcome Yet little known about interaction between SARS-CoV-2 innate immunity in this tissue. Here we apply single-cell RNA sequencing proteomics primary cell model human differentiated at air-liquid interface. demonstrates widespread tropism epithelial types. dominated by type I III...
At sites of inflammation, certain regulatory T cells (Treg cells) can undergo rapid reprogramming into helper-like without loss the transcription factor Foxp3. We show that is controlled by downregulation Eos (Ikzf4), an obligate corepressor for Reprogramming was restricted to a specific subset "Eos-labile" Treg present in thymus and identifiable characteristic surface markers DNA methylation. Mice made deficient this became impaired their ability provide help presentation new antigens naive...
The tumor microenvironment is profoundly immunosuppressive. We show that multiple types create intratumoral immune suppression driven by a specialized form of regulatory T cell (Treg) activation dependent on the PTEN (phosphatase and tensin homolog) lipid phosphatase. acted to stabilize Tregs in tumors, preventing them from reprogramming into inflammatory effector cells. In mice with Treg-specific deletion PTEN, tumors grew slowly, were inflamed, could not an immunosuppressive...
Abstract Cytosolic DNA sensing via the stimulator of IFN genes (STING) adaptor incites autoimmunity by inducing type I (IFN-αβ). In this study, we show that is also sensed STING to suppress immunity IDO. gene ablation abolished IFN-αβ and IDO induction dendritic cells (DCs) after nanoparticle (DNP) treatment. Marginal zone macrophages, some DCs, myeloid ingested DNPs, but CD11b+ DCs were only express IFN-β, whereas non-DCs major IL-1β producers. DNP-induced regulatory responses T cells,...
Cancer-associated lymphatic endothelial cells (LECs) are an active barrier to the effector arm of anti-tumor immune response; however, it remains unclear how LECs become immunosuppressive in tumor microenvironment (TME). Exosomal microRNAs (miRNAs) have recently been implicated intercellular crosstalk within TME. Here, we report a mechanistic model via which cervical cancer-secreted, exosome-encapsulated microRNA (miR)-1468-5p promotes PD-L1 upregulation and lymphangiogenesis impair T cell...
Hepatocellular carcinoma (HCC) is the major form of liver cancer for which there no effective therapy. Genetic modification with T‐cell receptors (TCRs) specific HCC‐associated antigens, such as α‐fetoprotein (AFP), can potentially redirect human T cells to specifically recognize and kill HCC tumor achieve antitumor effects. In this study, using lentivector peptide immunization, we identified a population cluster differentiation 8 (CD8) in leukocyte antigen (HLA)‐A2 transgenic AAD mice that...
Abstract Clinical response to immunotherapy is closely associated with the immunosuppressive tumour microenvironment (TME), and influenced by dynamic interaction between cells lymphatic endothelial (LECs). Here, we show that high levels of miR-142-5p positively correlate indoleamine 2,3-dioxygenase (IDO) expression in tumour-associated vessels advanced cervical squamous cell carcinoma (CSCC). The transferred CSCC-secreted exosomes into LECs exhaust CD8 + T via up-regulation IDO expression,...
ABSTRACT Under conditions of high antigenic load during infection with invasive lymphocytic choriomeningitis virus (LCMV) strains, can persist by selective clonal exhaustion antigen-specific CD8 + T cells. In this work we studied the down-regulation virus-specific -T-cell response a persistent adult mice, particular emphasis on contribution interferon in promoting host defense. Studies were conducted infecting mice deficient receptors for type I (alpha/beta [IFN-α/β]), II (IFN-γ), and both...
Abstract The rapid synthesis of heat shock proteins (Hsps) in cells subjected to environmental challenge is controlled by transcription factor‐1 (Hsf1). Regulation Hsps Hsf1 highly complex and, the whole organism, remains largely unexplored. In this study, we have used mouse embryo fibroblasts and bone marrow progenitor from hsf1 −/− mice as well hsp70.3 ‐ lacZ knock‐in bred on deficient genetic background ( +/− ), further elucidate function its participation a transcriptional activator...
The murine hsp70 gene family includes the evolutionarily conserved hsp70.1 andhsp70.3 genes, which are major proteins induced by heat and other stress stimuli.hsp70.1 encode identical protect cells facilitate their recovery from stress-induced damage. While has been widely studied roles of it encodes as molecular chaperones in a range human pathologies appreciated, little is known about developmental regulation expression vivo biological function products. To directly study physiological...
Abstract Cytosolic DNA sensing activates the stimulator of IFN genes (STING) adaptor to induce type I (IFN-αβ) production. Constitutive sustained STING activation incites tolerance breakdown, leading autoimmunity. In this study, we show that systemic treatments with nanoparticles (DNPs) induced potent immune regulatory responses via signaling suppressed experimental autoimmune encephalitis (EAE) when administered mice after immunization myelin oligodendrocyte glycoprotein (MOG), at EAE...
Activated inflammatory macrophages can express indoleamine 2,3-dioxygenase (IDO) and thus actively deplete their own tryptophan supply; however, it is not clear how amino acid depletion influences macrophage behavior in environments. In this report, we demonstrate that the stress response kinase GCN2 promotes inflammation mortality a mouse model of septicemia. vitro, enzymatic consumption enhanced sensitivity to Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) with significantly...
Background Activating the Stimulator of Interferon Genes (STING) adaptor incites antitumor immunity against immunogenic tumors in mice, prompting clinical trials to test STING activators. However, signaling tumor microenvironment (TME) during development Lewis lung carcinoma (LLC) suppresses promote growth. We hypothesized that local immune balance favoring suppression also attenuates responses following activation. The purpose this study was evaluate how activation impacts mice bearing LLC...
Abstract Purpose: Multisite stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) has demonstrated safety in advanced solid tumors (ASTs). However, no studies have examined the relationships between irradiated tumor response, SBRT-induced gene expression, and overall survival (OS). Patients Methods: with AST received SBRT (30–50 Gy 3–5 fractions) to two four metastases (200 mg i.v. every 3 weeks). was prescribed a maximum volume of 65 mL. Small complete coverage (complete-Rx),...
Abstract Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma (HCC) are urgently needed. The common cytokine receptor γ chain (γ c ) family cytokines IL-2, IL-7, IL-15 and IL-21 play fundamental roles development, differentiation effector phases. This study aims determine the combination effects of against HCC investigate optimized strategies utilize effect signal therapy. antitumor function AFP-specific receptor-engineered cells (TCR-T) was...
Abstract The mammalian small heat shock protein (sHSPs) family is comprised of 10 members and includes HSPB1, which proposed to play an essential role in cellular physiology, acting as a molecular chaperone regulate diverse processes. Whilst differential roles for sHSPs are suggested specific tissues, the relative contribution individual sHSP organ physiology remains unclear. To address function HSPB1 vivo determine its tissue‐specific expression during development adult, we generated...