3,695 results match your criteria expression granzyme

Intratumoral Foxp3RORγt T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients.

Cancer Immunol Immunother 2021 May 12. Epub 2021 May 12.

Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.

Background: Foxp3RORγt T cells possess both characteristics of regulatory T cells and T helper 17 cells and show significant immunoregulatory functions in autoimmune diseases. However, the role and clinical significance of Foxp3RORγt T cells in gastric cancer remains unclear.

Methods: We enrolled 452 gastric cancer tissue microarray samples and 60 fresh tumor tissue samples from Zhongshan Hospital. Read More

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Tissue-Resident Memory-Like CD8 T Cells Exhibit Heterogeneous Characteristics in Tuberculous Pleural Effusion.

J Immunol Res 2021 22;2021:6643808. Epub 2021 Apr 22.

Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China.

Tissue-resident memory T (T) cells are well known to play critical roles in peripheral tissues during virus infection and tumor immunology. Our previous studies indicated that CD69CD4 and CD69CD8 T cells in tuberculous pleural effusion (TPE) were antigen-specific memory T cells. However, the phenotypical and functional characteristics of CD8 T cells in tuberculosis remain unknown. Read More

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Blockade of transforming growth factor β2 by anti-sense oligonucleotide improves immunotherapeutic potential of IL-2 against melanoma in a humanized mouse model.

Cytotherapy 2021 May 9. Epub 2021 May 9.

Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea. Electronic address:

Background Aims: IL-2 is a potent cytokine that activates natural killer cells and CD8+ cytotoxic T lymphocytes (CTLs) and has been approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma. However, the medical use of IL-2 is restricted because of its narrow therapeutic window and potential side effects, including the expansion of regulatory T cells (Tregs).

Methods: In this study, the authors investigated the complementary effects of transforming growth factor-β2 (TGF-β2) anti-sense oligodeoxynucleotide (TASO) on the immunotherapeutic potential of IL-2 in a melanoma-bearing humanized mouse model. Read More

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Endometrial Cancer Suppresses CD8+ T Cell-Mediated Cytotoxicity in Postmenopausal Women.

Front Immunol 2021 23;12:657326. Epub 2021 Apr 23.

Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.

Endometrial cancer is the most common gynecological cancer. To investigate how it suppresses host immune function, we isolated CD8+ T cells from endometrial endometroid carcinomas and adjacent non-cancerous endometrium and determined if the tumor environment regulates cytotoxic capacity. Endometrial carcinomas had increased numbers of CD8+ T cells compared to adjacent non-cancerous endometrium. Read More

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A subset of cytotoxic effector memory T cells enhances CAR T cell efficacy in a model of pancreatic ductal adenocarcinoma.

Sci Transl Med 2021 May;13(592)

Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.

In humans, the natural killer (NK) cell marker CD161 identifies several subsets of T cells, including a polyclonal CD8 αβ T cell receptor-expressing subset with characteristic specificity for tissue-localized viruses. This subset also displays enhanced cytotoxic and memory phenotypes. Here, we characterized this unique T cell subset and determined its potential suitability for use in chimeric antigen receptor (CAR) T cell therapy. Read More

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Histomorphological patterns of regional lymph nodes in COVID-19 lungs.

Pathologe 2021 May 5. Epub 2021 May 5.

Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.

Background: A dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, and aberrant antigen presentation.

Objectives: To understand the heterogeneity of immune response in COVID-19, a thorough investigation of histomorphological patterns in regional lymph nodes was performed. Read More

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Non-Malignant CD30+ Cells in Contralateral Peri-Implant Capsule of Patient With BIA-ALCL: A Premalignant Step?

Aesthet Surg J 2021 May 4. Epub 2021 May 4.

Department of Medicine, Brown University Alpert Medical School, Providence, RI.

CD30 lymphocyte activation antigen and phosphorylated STAT3 (pSTAT3) are consistent markers of tumor cells in breast implant associated anaplastic large cell lymphoma (BIA-ALCL). We present a case of BIA-ALCL in a breast implant capsule containing clustered tumor cells expressing CD30, pSTAT3, pSTAT6, IL-9 and Granzyme B tumor cell biomarkers. Remarkably, the contralateral breast contained many scattered CD30+ large, atypical cells surrounded by inflammatory cells raising a suspicion of bilateral BIA-ALCL, known to occur in some patients. Read More

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5,-ALA/SFC enhanced the antitumor effects of PD-L1 blockade via regulated exhaustion T cell metabolism in melanoma model.

Cancer Sci 2021 May 2. Epub 2021 May 2.

Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.

Mitochondria are key cytoplasmic organelles. Their activation is critical for the generation of T-cell proliferation and cytotoxicity. Exhausted tumor infiltrating T cells show a decreased mitochondrial function and mass. Read More

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A combination of the percentages of IFN-γCD4T cells and granzyme BCD19B cells is associated with acute hepatic rejection: a case control study.

J Transl Med 2021 May 1;19(1):187. Epub 2021 May 1.

Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongtinan Road, Chaoyang District, Beijing, 100020, China.

Background: T cells and B cells play a key role in alloimmune responses. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prognostic marker.

Methods: Blood samples together with the clinical data from liver transplant recipients with and without acute hepatic rejection were collected and analyzed as well as from a validation cohort. Read More

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Regulatory T Cells as an Escape Mechanism to the Immune Response in Infection.

Front Cell Infect Microbiol 2021 13;11:630583. Epub 2021 Apr 13.

Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan, Mexico.

Murine cysticercosis by is a model for human neurocysticercosis. Genetic and/or immune differences may underlie the higher susceptibility to infection in BALB/cAnN with respect to C57BL/6 mice. T regulatory cells (Tregs) could mediate the escape of from the host immunity. Read More

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Clinical Activity of an hTERT-Specific Cancer Vaccine (Vx-001) in "Immune Desert" NSCLC.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

Vaxon Biotech, 75005 Paris, France.

Background: Tumors can be separated into immunogenic/hot and non-immunogenic/cold on the basis of the presence of tumor-infiltrating lymphocytes (TILs), the expression of PD-L1 and the tumor mutation burden (TMB). In immunogenic tumors, TILs become unable to control tumor growth because their activity is suppressed by different inhibitory pathways, including PD-1/PD-L1. We hypothesized that tumor vaccines may not be active in the immunosuppressive microenvironment of immunogenic/hot tumors while they could be efficient in the immune naïve microenvironment of non-immunogenic/cold tumors. Read More

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Plasma-Activated Medium Potentiates the Immunogenicity of Tumor Cell Lysates for Dendritic Cell-Based Cancer Vaccines.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

Department for Immunology and Immunoparasitology, Institute for the Application of Nuclear Energy, University of Belgrade, 11080 Belgrade, Serbia.

Autologous dendritic cells (DCs)-based vaccines are considered quite promising for cancer immunotherapy due to their exquisite potential to induce tumor antigen-specific cytotoxic T cells. However, a lack of efficient protocols for inducing immunogenic tumor antigens limits the efficacy of DC-based cancer vaccines. Here, we found that a plasma-activated medium (PAM) induces immunogenic cell death (ICD) in tumor cells but not in an immortalized L929 cell line or human peripheral blood mononuclear cells. Read More

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Carbamazepine Induces Focused T Cell Responses in Resolved Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Cases But Does Not Perturb the Immunopeptidome for T Cell Recognition.

Front Immunol 2021 12;12:653710. Epub 2021 Apr 12.

Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.

Antiseizure medications (ASMs) are frequently implicated in T cell-mediated drug hypersensitivity reactions and cause skin tropic pathologies that range in severity from mild rashes to life-threatening systemic syndromes. During the acute stages of the more severe manifestations of these reactions, drug responsive proinflammatory CD8 T cells display classical features of Th1 cytokine production ( IFNγ) and cytolysis ( granzyme B, perforin). These T cells may be found locally at the site of pathology ( blister cells/fluid), as well as systemically ( blood, organs). Read More

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Natural Killer Cell Group 7 Sequence in Cytotoxic Cells Optimizes Exocytosis of Lytic Granules Essential for the Perforin-Dependent, but Not Fas Ligand-Dependent, Cytolytic Pathway.

Immunohorizons 2021 Apr 28;5(4):234-245. Epub 2021 Apr 28.

Department of Immunology, Kitasato University School of Medicine, Kanagawa, Japan; and

Cytotoxic cells, such as CD8 T cells or NK cells, have been shown to eliminate virus-infected cells or transformed cells primarily via two pathways: the perforin/granzyme-dependent pathway and the Fas ligand-Fas pathway; however, the precise cytolytic mechanisms have not been clarified thoroughly. In our previous study, we demonstrated that a T-box transcription factor, Eomesodermin (Eomes), may play important roles in activating the perforin pathway besides inducing perforin and granzyme B mRNA expression. In this study, we identified natural killer cell group 7 sequence (Nkg7), a molecule induced by Eomes, to be found critical for perforin-dependent cytolysis. Read More

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HLA-A2.1-restricted ECM1-derived epitope LA through DC cross-activation priming CD8 T and NK cells: a novel therapeutic tumour vaccine.

J Hematol Oncol 2021 Apr 28;14(1):71. Epub 2021 Apr 28.

Department of Pharmacology, School of Pharmacy, China Medical University, No. 13, Beihai Road, Dadong District, Shenyang, Liaoning Province, China.

Background: CD8 T cell-mediated adaptive cellular immunity and natural killer (NK) cell-mediated innate immunity both play important roles in tumour immunity. This study aimed to develop therapeutic tumour vaccines based on double-activation of CD8 T and NK cells.

Methods: The immune Epitope database, Molecular Operating Environment software, and enzyme-linked immunosorbent assay were used for epitope identification. Read More

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Analysis of the Long-Term Impact on Cellular Immunity in COVID-19-Recovered Individuals Reveals a Profound NKT Cell Impairment.

mBio 2021 04 27;12(2). Epub 2021 Apr 27.

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected over 120 million people and killed over 2.7 million individuals by March 2021. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remain to be analyzed. Read More

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Functional responsiveness of memory T cells from COVID-19 patients.

Cell Immunol 2021 Apr 17;365:104363. Epub 2021 Apr 17.

Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey. Electronic address:

The presence of memory T cells in COVID-19 patients has been acknowledged, however the functional potency of memory responses is critical for protection. In this study, naïve, effector, effector memory, and central memory CD4 and CD8 T cells obtained from the COVID-19 survivors were re-exposed to autologous monocyte-derived DCs that were loaded with SARS-CoV-2 spike glycoprotein S1. Proliferation capacity, CD25, 4-1BB, and PD-1 expression, and IFN-γ, IL-6, granzyme, granulysin, and FasL secretion were enhanced in CD4 and CD8 effector memory and central memory T cells. Read More

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Inflammatory Status Might Direct ILC and NK Cells to IL-17 expressing ILC3 and NK Subsets in Behcet's Disease.

Immunol Lett 2021 Apr 23. Epub 2021 Apr 23.

Department of Immunology, Aziz Sancar Institute of Experimental Medicine (Aziz Sancar DETAE), Istanbul University, Istanbul, Turkey. Electronic address:

Innate lymphoid cells (ILCs) are lymphoid cells that have important effector and regulatory functions in innate immunity and tissue remodeling. Uncontrolled activation and proliferation of ILCs can contribute to inflammatory autoimmune diseases. Behcet's disease (BD) is a complex systemic inflammatory disorder of unknown etiology. Read More

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Robust hepatitis B vaccine-reactive T cell responses in failed humoral immunity.

Mol Ther Methods Clin Dev 2021 Jun 23;21:288-298. Epub 2021 Mar 23.

University Hospital Marien Hospital Herne, Ruhr-University of Bochum, Bochum, Germany.

While virus-specific antibodies are broadly recognized as correlates of protection, virus-specific T cells are important for direct clearance of infected cells. Failure to generate hepatitis B virus (HBV)-specific antibodies is well-known in patients with end-stage renal disease. However, whether and to what extent HBV-specific cellular immunity is altered in this population and how it influences humoral immunity is not clear. Read More

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Long Non-coding RNA LINC02474 Affects Metastasis and Apoptosis of Colorectal Cancer by Inhibiting the Expression of GZMB.

Front Oncol 2021 9;11:651796. Epub 2021 Apr 9.

Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies. Metastasis is the main event that impedes the therapeutic effect on CRC, and its underlying mechanisms remain largely unclear. LINC02474 is a novel long noncoding RNA (lncRNA) associated with metastasis of CRC, while little is known about how LINC02474 regulates these malignant characteristics. Read More

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Correlation of Regulatory T Cell Numbers with Disease Tolerance upon Virus Infection.

Immunohorizons 2021 Apr 23;5(4):157-169. Epub 2021 Apr 23.

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA;

The goal of a successful immune response is to clear the pathogen while sparing host tissues from damage associated with pathogen replication and active immunity. Regulatory T cells (Treg) have been implicated in maintaining this balance as they contribute both to the organization of immune responses as well as restriction of inflammation and immune activation to limit immunopathology. To determine if Treg abundance prior to pathogen encounter can be used to predict the success of an antiviral immune response, we used genetically diverse mice from the collaborative cross infected with West Nile virus (WNV). Read More

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Immuno-profiling and cellular spatial analysis using five immune oncology multiplex immunofluorescence panels for paraffin tumor tissue.

Sci Rep 2021 Apr 19;11(1):8511. Epub 2021 Apr 19.

Department of Translational Molecular Pathology, Unit 951, The University of Texas MD Anderson Cancer Center, 2130 Holcombe Blvd., Houston, TX, 77030, USA.

Multiplex immunofluorescence (mIF) has arisen as an important tool for immuno-profiling tumor tissues. We updated our manual protocol into an automated protocol that allows the use of up to seven markers in five mIF panels to apply to formalin-fixed paraffin-embedded tumor tissues. Using a tyramide signal amplification system, we optimized five mIF panels that included cytokeratin to characterize malignant cells (MCs), immune checkpoint markers (i. Read More

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Select antitumor cytotoxic CD8 T clonotypes expand in patients with chronic lymphocytic leukemia treated with ibrutinib.

Clin Cancer Res 2021 Apr 19. Epub 2021 Apr 19.

Hematology Branch, National Heart Lung and Blood Institute

Purpose: In chronic lymphocytic leukemia (CLL), the T-cell receptor (TCR) repertoire is skewed and tumor-derived antigens are hypothesized as drivers of oligoclonal expansion. Ibrutinib, a standard treatment for CLL, inhibits not only Bruton tyrosine kinase of the B-cell receptor signaling pathway, but also interleukin-2-inducible kinase of the TCR signaling pathway. T-cell polarization and activation are affected by ibrutinib, but it is unknown if T cells contribute to clinical response. Read More

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Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction.

Environ Health Prev Med 2021 Apr 19;26(1):50. Epub 2021 Apr 19.

Department of Hygiene, Kawasaki Medical School, Kurashiki, 701-0192, Japan.

Background: Asbestos fibers possess tumorigenicity and are thought to cause mesothelioma. We have previously reported that exposure to asbestos fibers causes a reduction in antitumor immunity. Asbestos exposure in the mixed lymphocyte reaction (MLR) showed suppressed induction of cytotoxic T lymphocytes (CTLs), accompanied by a decrease in proliferation of CD8 T cells. Read More

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Interaction Networks Converging on Immunosuppressive Roles of Granzyme B: Special Niches Within the Tumor Microenvironment.

Front Immunol 2021 1;12:670324. Epub 2021 Apr 1.

School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, China.

Granzyme B is a renowned effector molecule primarily utilized by CTLs and NK cells against ill-defined and/or transformed cells during immunosurveillance. The overall expression of granzyme B within tumor microenvironment has been well-established as a prognostic marker indicative of priming immunity for a long time. Until recent years, increasing immunosuppressive effects of granzyme B are unveiled in the setting of different immunological context. Read More

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PMMA-Based Continuous Hemofiltration Modulated Complement Activation and Renal Dysfunction in LPS-Induced Acute Kidney Injury.

Front Immunol 2021 1;12:605212. Epub 2021 Apr 1.

Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Science, University of Foggia, Foggia, Italy.

Sepsis-induced acute kidney injury (AKI) is a frequent complication in critically ill patients, refractory to conventional treatments. Aberrant activation of innate immune system may affect organ damage with poor prognosis for septic patients. Here, we investigated the efficacy of polymethyl methacrylate membrane (PMMA)-based continuous hemofiltration (CVVH) in modulating systemic and tissue immune activation in a swine model of LPS-induced AKI. Read More

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Intracellular expression of granzymes A, B, K and M in blood lymphocyte subsets of critically ill patients with or without sepsis.

Clin Exp Immunol 2021 Apr 18. Epub 2021 Apr 18.

Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Sepsis is a complex syndrome related to an infection-induced exaggerated inflammatory response, which is associated with a high mortality. Granzymes (gzm) are proteases mainly found in cytotoxic lymphocytes, that not only have a role in target cell death, but also as mediators of infection and inflammation. We here sought to analyse the intracellular expression of gzm A, B, M and K by flow cytometry in diverse blood lymphocyte populations from 22 sepsis patients, 12 non-infected ICU patients and 32 healthy controls. Read More

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Interruption of MDM2 signaling augments MDM2-targeted T cell-based antitumor immunotherapy through antigen-presenting machinery.

Cancer Immunol Immunother 2021 Apr 18. Epub 2021 Apr 18.

Department of Otolaryngology-Head & Neck Surgery, Asahikawa Medical University, Asahikawa, 078-8510, Japan.

Identification of immunogenic tumor antigens, their corresponding T cell epitopes and the selection of effective adjuvants are prerequisites for developing effective cancer immunotherapies such as therapeutic vaccines. Murine double minute 2 (MDM2) is an E3 ubiquitin-protein ligase that negatively regulates tumor suppressor p53. Because MDM2 overexpression serves as a poor prognosis factor in various types of tumors, it would be beneficial to develop MDM2-targeted cancer vaccines. Read More

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Interleukin-35 regulates peripheral T cell activity in patients with Kawasaki disease.

Int Immunopharmacol 2021 Apr 13;96:107642. Epub 2021 Apr 13.

Department of General Internal Medicine, The Children's Hospital Affiliated to Xi'an Jiaotong University (Xi'an Children's Hospital), Xi'an, Shaanxi Province 710003, China. Electronic address:

Interleukin-35 (IL-35) regulates immune cell function in inflammation, infection, cancer, and autoimmune diseases. However, the modulatory activity of IL-35 exerted on T cells is not fully understood in Kawasaki disease. For this purpose, the present study included 28 patients with Kawasaki disease and 16 healthy controls. Read More

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Hypoxia enhances the production and antitumor effect of exosomes derived from natural killer cells.

Ann Transl Med 2021 Mar;9(6):473

School of Pharmacy, Binzhou Medical University, Yantai, China.

Background: Exosomes are a subgroup of extracellular vesicles that are naturally released by almost all types of cells. However, the factors that promote the capacity of natural killer (NK) cells to release exosomes are unclear. In this study, we investigated whether hypoxia can enhance the yield of NK cell-derived exosomes and improve the immunotherapeutic effects of these cells. Read More

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