26,541 results match your criteria memory t-cell


Aging-dependent mitochondrial dysfunction mediated by ceramide signaling inhibits antitumor T cell response.

Cell Rep 2021 May;35(5):109076

Departments of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA. Electronic address:

We lack a mechanistic understanding of aging-mediated changes in mitochondrial bioenergetics and lipid metabolism that affect T cell function. The bioactive sphingolipid ceramide, induced by aging stress, mediates mitophagy and cell death; however, the aging-related roles of ceramide metabolism in regulating T cell function remain unknown. Here, we show that activated T cells isolated from aging mice have elevated C14/C16 ceramide accumulation in mitochondria, generated by ceramide synthase 6, leading to mitophagy/mitochondrial dysfunction. Read More

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The human anti-CD40 agonist antibody mitazalimab (ADC-1013; JNJ-64457107) activates antigen-presenting cells, improves expansion of antigen-specific T cells, and enhances anti-tumor efficacy of a model cancer vaccine in vivo.

Cancer Immunol Immunother 2021 May 5. Epub 2021 May 5.

Alligator Bioscience AB, Medicon Village, 223 81, Lund, Sweden.

Non-responders to checkpoint inhibitors generally have low tumor T cell infiltration and could benefit from immunotherapy that activates dendritic cells, with priming of tumor-reactive T cells as a result. Such therapies may be augmented by providing tumor antigen in the form of cancer vaccines. Our aim was to study the effects of mitazalimab (ADC-1013; JNJ-64457107), a human anti-CD40 agonist IgG1 antibody, on activation of antigen-presenting cells, and how this influences the priming and anti-tumor potential of antigen-specific T cells, in mice transgenic for human CD40. Read More

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Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells.

medRxiv 2021 Apr 27. Epub 2021 Apr 27.

Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. We evaluated 254 COVID-19 patients longitudinally from early infection and for eight months thereafter and found a predominant broad-based immune memory response. SARS-CoV-2 spike binding and neutralizing antibodies exhibited a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells. Read More

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Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence.

bioRxiv 2021 Apr 29. Epub 2021 Apr 29.

CD8+ T cells are important antiviral effectors that can potentiate long-lived immunity against COVID-19, but a detailed characterization of these cells has been hampered by technical challenges. We screened 21 well-characterized, longitudinally-sampled convalescent donors that recovered from mild COVID-19 against a collection of SARS-CoV-2 tetramers, and identified one participant with an immunodominant response against Nuc , a peptide that is conserved in all the SARS-CoV-2 variants-of-concern reported to date. We conducted 38- parameter CyTOF phenotyping on tetramer-identified Nuc -specific CD8+ T cells, and on CD4+ and CD8+ T cells recognizing the entire nucleocapsid and spike proteins from SARS- CoV-2, and took 32 serological measurements on longitudinal specimens from this participant. Read More

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CMV infection, CD19 B cell depletion, and Lymphopenia as predictors for unexpected admission in the institutionalized elderly.

Immun Ageing 2021 May 4;18(1):21. Epub 2021 May 4.

Institute of Public Health, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nong St, Taipei, 11221, Taiwan.

Background: Chronic infections played a detrimental role on health outcomes in the aged population, and had complex associations with lymphocyte subsets distribution. Our study aimed to explore the predictive roles of chronic infections, lymphopenia, and lymphocyte subsets on unexpected admission and mortality in the institutionalized oldest-old during 3 year follow-up period.

Results: There were 163 participants enrolled prospectively with median age of 87. Read More

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Age-Related Effects on Thymic Output and Homeostatic T Cell Expansion Following Depletional Induction in Renal Transplant Recipients.

Am J Transplant 2021 May 3. Epub 2021 May 3.

Duke Transplant Center, Department of Surgery, Duke University School of Medicine, Durham, NC, USA.

Thymic output and homeostatic mature cell proliferation both influence T-cell repopulation following depletional induction, though the relative contribution of each and their association with recipient age have not been well studied. We investigated the repopulating T-cell kinetics in kidney transplant recipients who underwent alemtuzumab induction followed by belatacept/rapamycin-based immunosuppression over 36 months posttransplantation. We focused specifically on the correlation between repopulating T cell subsets and the age of patients. Read More

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Inhibition of CDK4/6 promotes CD8 T-cell memory formation.

Cancer Discov 2021 May 3. Epub 2021 May 3.

Dana-Farber Cancer Institute

CDK4/6 inhibitors are approved to treat breast cancer and are in trials for other malignancies. We examined CDK4/6 inhibition in mouse and human CD8 T cells during early stages of activation. Mice receiving tumor-specific CD8 T cells treated with CDK4/6 inhibitors displayed increased T cell persistence and immunologic memory. Read More

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Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis.

Bioact Mater 2021 Nov 13;6(11):3879-3891. Epub 2021 Apr 13.

Academy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Tianjin University, 92 Weijin Road, Nankai District, Tianjin, 300072, China.

The conventional immunoadjuvants in vaccine have weak effect on stimulating antigen presentation and activating anti-tumor immunity. Unexpectedly, we discovered that non-pathogenic Sendai virus (SeV) could activate antigen-presenting cells (APCs) represented by dendritic cells (DCs). Here, we designed an injectable SeV-based hydrogel vaccine (SHV) to execute multi-channel recruitment and stimulation of DCs for boosting the specific immune response against tumors. Read More

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November 2021

Uremia-Associated Immunological Aging and Severity of COVID-19 Infection.

Front Med (Lausanne) 2021 14;8:675573. Epub 2021 Apr 14.

Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, Netherlands.

One year after the start of the COVID-19 pandemic it has become clear that some groups of individuals are at particular high risk of a complicated course of infection resulting in high morbidity and mortality. Two specific risk factors are most prominent, old age and the presence of co-morbidity. Recent studies have shown that patients with compromised renal function, especially those treated with renal replacement therapy or having received a kidney transplant are at a much higher risk for severe COVID infection and increased mortality. Read More

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Role of Circulating T Follicular Helper Cells and Stem-Like Memory CD4 T Cells in the Pathogenesis of HIV-2 Infection and Disease Progression.

Front Immunol 2021 16;12:666388. Epub 2021 Apr 16.

Department of HIV/AIDS, National Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, India.

CD4 T cells are critical players in the host adaptive immune response. Emerging evidence suggests that certain CD4 T cell subsets contribute significantly to the production of neutralizing antibodies and help in the control of virus replication. Circulating T follicular helper cells (Tfh) constitute a key T cell subset that triggers the adaptive immune response and stimulates the production of neutralizing antibodies (NAbs). Read More

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CMV Status Drives Distinct Trajectories of CD4+ T Cell Differentiation.

Front Immunol 2021 15;12:620386. Epub 2021 Apr 15.

Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA, United States.

Cytomegalovirus (CMV) is one of the most commonly recognized opportunistic pathogens and remains the most influential known parameter in shaping an individual's immune system. As such, T cells induced by CMV infection could have a long-term impact on subsequent immune responses. Accumulating evidence indicates that memory T cells developed during past bacterial and viral infection can cross-react with unrelated pathogens, including transplant antigens, and can alter responses to infections, vaccines, cancers, or rejection. Read More

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Immuno-oncology for B-cell lymphomas.

Authors:
Yoon Seok Choi

Blood Res 2021 Apr;56(S1):S70-S74

Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea.

The goal of cancer immunotherapy is to restore and optimize the immune response against malignant clones through several stages, from recognition of tumor antigens to establishment of long-lived memory cell populations. Boosting the intrinsic anti-tumor immune responses of the patients' own, several types of "active immunotherapies" have been tried in many types of malignancies, inspired by successful experiences of immune checkpoint inhibition even in Hodgkin lymphoma. However, in B-cell non-Hodgkin lymphomas, clinical usefulness of such "active immunotherapies" is relatively unsatisfactory considering the remarkable advances in "passive immunotherapy," including CD19-targeting chimeric antigen receptor T-cell therapy. Read More

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Recent advances on smart glycoconjugate vaccines in infections and cancer.

FEBS J 2021 May 2. Epub 2021 May 2.

Amsterdam UMC, Vrije Universiteit Amsterdam, department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam, Netherlands.

Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the Human Immunodeficiency Virus or to induce cellular T cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Read More

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Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose.

Science 2021 Apr 30. Epub 2021 Apr 30.

Department of Infectious Disease, Imperial College London, London, UK.

SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. Read More

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Gold nanoparticles (AuNPs) impair LPS-driven immune responses by promoting a tolerogenic-like dendritic cell phenotype with altered endosomal structures.

Nanoscale 2021 Apr;13(16):7648-7666

Department of Biosciences, Paris-Lodron University Salzburg, Hellbrunner Str. 34, 5020 Salzburg, Austria.

Dendritic cells (DCs) shape immune responses by influencing T-cell activation. Thus, they are considered both an interesting model for studying nano-immune interactions and a promising target for nano-based biomedical applications. However, the accentuated ability of nanoparticles (NPs) to interact with biomolecules may have an impact on DC function that poses an unexpected risk of unbalanced immune reactions. Read More

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The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children.

Transplant Direct 2021 May 23;7(5):e693. Epub 2021 Apr 23.

Laboratory of Immune-regulation, Immunology Department, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain.

Regulatory T cells (Treg) are crucial for the induction and maintenance of graft tolerance. In pediatric heart transplant procedures, the thymus is routinely excised, removing the primary source of T-cell replenishment. Consequently, thymectomy joined to the effects of immunosuppression on the T-cell compartment may have a detrimental impact on Treg values, compromising the intrinsic tolerance mechanisms and the protective role of Treg preventing graft rejection in heart transplant children. Read More

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T Cell-Mediated Immune Responses to AAV and AAV Vectors.

Front Immunol 2021 13;12:666666. Epub 2021 Apr 13.

Wistar Institute, Philadelphia, PA, United States.

Adeno-associated virus (AAV)-mediated gene transfer has benefited patients with inherited diseases, such as hemophilia B, by achieving long-term expression of the therapeutic transgene. Nevertheless, challenges remain due to rejection of AAV-transduced cells, which in some, but not all, patients can be prevented by immunosuppression. It is assumed that CD8 T cells induced by natural infections with AAVs are recalled by the AAV vector's capsid and upon activation eliminate cells expressing the degraded capsid antigens. Read More

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Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment.

Sci Rep 2021 Apr 29;11(1):9299. Epub 2021 Apr 29.

Immunology Department, Ramón y Cajal University Hospital, IRYCIS, REEM, Ctra. Colmenar Km. 9.100, 28034, Madrid, Spain.

Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing-remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Read More

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Tinkering under the Hood: Metabolic Optimisation of CAR-T Cell Therapy.

Antibodies (Basel) 2021 Apr 26;10(2). Epub 2021 Apr 26.

Institute of Life Science, Swansea University Medical School, Swansea University, Swansea SA2 8PP, UK.

Chimeric antigen receptor (CAR)-T cells are one of the most exciting areas of immunotherapy to date. Clinically available CAR-T cells are used to treat advanced haematological B-cell malignancies with complete remission achieved at around 30-40%. Unfortunately, CAR-T cell success rates are even less impressive when considering a solid tumour. Read More

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Pattern of Tumor-Infiltrating Lymphocytes in Mixed Epithelial and Stromal Tumor of the Kidney: A Review of Five Cases.

Cells 2021 Apr 16;10(4). Epub 2021 Apr 16.

Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Mixed epithelial and stromal tumor of the kidney (MESTK), a benign rare tumor with malignant transformation potential, is thought to be derived from fetal or immature cells originating from the mesonephric and Müllerian ducts. However, due to its rarity, little is known about the anti-tumor immune responses in MESTK. Herein, we present five cases of MESTK and evaluate the population of tumor-infiltrating lymphocytes (TILs) using a freshly obtained MESTK sample. Read More

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Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8 T Cell Response in Hepatocellular Carcinoma.

Cancers (Basel) 2021 Apr 16;13(8). Epub 2021 Apr 16.

Translational Hepatology Unit, Guadalajara University Hospital, 19002 Gudalajara, Spain.

Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens or aberrantly expressed host's antigens, but they become progressively exhausted or deleted. Read More

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Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells.

Viruses 2021 Apr 25;13(5). Epub 2021 Apr 25.

Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA.

The viral antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress the human immunodeficiency virus (HIV) infection. Read More

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TGF-β: Many Paths to CD103 CD8 T Cell Residency.

Cells 2021 Apr 23;10(5). Epub 2021 Apr 23.

Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.

CD8 tissue-resident memory T (T) cells primarily reside in nonlymphoid tissues without recirculating and provide front-line protective immunity against infections and cancers. CD8 T cells can be generally divided into CD69 CD103 T cells (referred to as CD103 T cells) and CD69 CD103 T cells (referred to as CD103 T cells). TGF-β plays a critical role in the development and maintenance of CD103 CD8 T cells. Read More

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Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma.

Authors:
Fatih M Uckun

Cancers (Basel) 2021 Apr 22;13(9). Epub 2021 Apr 22.

Norris Comprehensive Cancer Center and Childrens Center for Cancer and Blood Diseases, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA 90027, USA.

SeverFigurel cellular elements of the bone marrow (BM) microenvironment in multiple myeloma (MM) patients contribute to the immune evasion, proliferation, and drug resistance of MM cells, including myeloid-derived suppressor cells (MDSCs), tumor-associated M2-like, "alternatively activated" macrophages, CD38+ regulatory B-cells (Bregs), and regulatory T-cells (Tregs). These immunosuppressive elements in bidirectional and multi-directional crosstalk with each other inhibit both memory and cytotoxic effector T-cell populations as well as natural killer (NK) cells. Immunomodulatory imide drugs (IMiDs), protease inhibitors (PI), monoclonal antibodies (MoAb), adoptive T-cell/NK cell therapy, and inhibitors of anti-apoptotic signaling pathways have emerged as promising therapeutic platforms that can be employed in various combinations as part of a rationally designed immunomodulatory strategy against an immunosuppressive tumor microenvironment (TME) in MM. Read More

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Role of Myeloid Cells in Oncolytic Reovirus-Based Cancer Therapy.

Viruses 2021 04 10;13(4). Epub 2021 Apr 10.

Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada.

Oncolytic reovirus preferentially targets and kills cancer cells via the process of oncolysis, and additionally drives clinically favorable antitumor T cell responses that form protective immunological memory against cancer relapse. This two-prong attack by reovirus on cancers constitutes the foundation of its use as an anticancer oncolytic agent. Unfortunately, the efficacy of these reovirus-driven antitumor effects is influenced by the highly suppressive tumor microenvironment (TME). Read More

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Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly.

Cells 2021 Apr 8;10(4). Epub 2021 Apr 8.

Department of Exercise Physiology and Sports Therapy, Institute of Sports Science, Justus-Liebig-University Gießen, 35394 Gießen, Germany.

With increasing age, the immune system undergoes a remodeling process, affecting the shift of T cell subpopulations and the development of chronic low-grade inflammation. Clinically, this is characterized by increased susceptibility to infections or development of several diseases. Since lifestyle factors can play a significant role in reducing the hallmarks of immune aging and inflammation, we investigated the effect of a 6 week low-dose combined resistance and endurance training program. Read More

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Rational Vaccine Design in Times of Emerging Diseases: The Critical Choices of Immunological Correlates of Protection, Vaccine Antigen and Immunomodulation.

Pharmaceutics 2021 Apr 6;13(4). Epub 2021 Apr 6.

School of Biomolecular and Biomedical Sciences, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.

Vaccines are the most effective medical intervention due to their continual success in preventing infections and improving mortality worldwide. Early vaccines were developed empirically however, rational design of vaccines can allow us to optimise their efficacy, by tailoring the immune response. Establishing the immune correlates of protection greatly informs the rational design of vaccines. Read More

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CD4+ and CD8+ Circulating Memory T Cells Are Crucial in the Protection Induced by Vaccination with Typhi Porins.

Microorganisms 2021 Apr 7;9(4). Epub 2021 Apr 7.

Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional "Siglo XXI", Instituto Mexicano del Seguro Social (IMSS), Cuauhtemoc, Ciudad de Mexico 06720, Mexico.

serovar Typhi (. Typhi) porins, OmpC and OmpF, are potent inducers of the immune response against . Typhi in mice and humans. Read More

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Improving anti-PD-L1 therapy in triple negative breast cancer by polymer-enhanced immunogenic cell death and CXCR4 blockade.

J Control Release 2021 Apr 27;334:248-262. Epub 2021 Apr 27.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address:

Triple negative breast cancer (TNBC) with highly metastatic features generally does not respond to anti-programmed cell death 1 ligand 1 (PD-L1) therapy due to multiple immunosuppressive mechanisms to exclude and disable T cells. Here, we develop a polymer-based combinatory approach consisting of both immunogenic cell death (ICD)-inducing and CXCR4-inhibiting function to prime tumor microenvironment and improve anti-PD-L1 therapy in TNBC. Our findings revealed that the combination therapy was able to spur the T cell response in primary tumors by increasing the tumor immunogenicity to recruit T cells, removing the physiological barriers of intratumoral fibrosis and collagen to increase T cell infiltration, and reducing the immunosuppressive cells to revive T cells. Read More

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Detection of CAR-T19 cells in peripheral blood and cerebrospinal fluid: An assay applicable to routine diagnostic laboratories.

Cytometry B Clin Cytom 2021 Apr 29. Epub 2021 Apr 29.

Department of Haematology, University Hospitals and Weston NHS Foundation Trust, Bristol, United Kingdom.

Background: Chimeric antigen receptor-modified T-cells targeting CD19 (CAR-T19) are licensed for treating relapsed/refractory diffuse large B-cell lymphoma and B-acute lymphoblastic leukemia. Predicting treatment responses and toxicity (e.g. Read More

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