1,711 results match your criteria Immunotherapeutic Targeting

Exploring the role of immunotherapeutic drugs in autoimmune diseases: A comprehensive review.

J Oral Biol Craniofac Res 2021 Apr-Jun;11(2):291-296. Epub 2021 Feb 23.

Department of Oral Medicine & Radiology, Government Dental College & Hospital, Nagpur, Maharashtra, India.

Autoimmune diseases are group of disorders where an immune response is mounted against the self. The prevalence and burden of this well established and recognised entity is on the rise. Irrespective of being a systemic or organ specific autoimmune disorder, the common underlying mechanism of action, is the imbalance in immune system resulting in loss of tolerance to self-antigens. Read More

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February 2021

Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis.

Front Oncol 2021 16;11:562315. Epub 2021 Apr 16.

Department of Medical Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Background: Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have demonstrated promise in treating a variety of advanced cancers; however, little is known regarding their efficacy under various clinical situations, including different cancer types, treatment lines, drug combinations, and therapeutic regimens.

Methods: Published articles and conference abstracts (in English) in PubMed, Embase, the Cochrane Central Register, and Web of Science were searched up to February 10, 2020. The data were analyzed by the meta-analysis program in Stata. Read More

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Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.

Cochrane Database Syst Rev 2021 04 30;4:CD013257. Epub 2021 Apr 30.

Department of Thoracic Oncology, University Hospital of Besançon, Besançon, France.

Background: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have changed the first-line treatment of people with advanced non-small cell lung cancer (NSCLC). Single-agent pembrolizumab (a PD-1 inhibitor) is currently the standard of care as monotherapy in patients with PD-L1 expression ≥ 50%, either alone or in combination with chemotherapy when PD-L1 expression is less than 50%. Atezolizumab (PD-L1 inhibitor) has also been approved in combination with chemotherapy and bevacizumab (an anti-angiogenic antibody) in first-line NSCLC regardless of PD-L1 expression. Read More

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LAMP-5 is an essential inflammatory-signaling regulator and novel immunotherapy target for Mixed Lineage Leukemia-Rearranged acute leukemia.

Haematologica 2021 Apr 29. Epub 2021 Apr 29.

Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA; Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH, 45229.

Although great advances have been made in understanding the pathobiology of MLL-rearranged (MLL-r) leukemias, therapies for this leukemia have remained limited, and clinical outcomes remain bleak. To identify novel targets for immunotherapy treatments, we compiled a lineage-independent MLL-r leukemia gene signature using publicly available data sets. Data from large leukemia repositories were filtered through the In-silico Human Surfaceome, providing a list of highly predicted cell surface proteins overexpressed in MLL-r leukemias. Read More

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[Preparation of a novel tri-specific T cell engager targeting CD19 antigen and its anti-leukemia effect exploration].

Zhonghua Xue Ye Xue Za Zhi 2021 Mar;42(3):217-223

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Peking Union Medical University, CAMS & PUMC, Tianjin 300020, China.

To prepare a novel tri-specific T cell engager (19TriTE) targeting CD19 antigen, and to investigate its immunotherapeutic effect on CD19-positive hematological malignancies. 19TriTE was constructed by molecular cloning technology and successfully expressed through the eukaryotic expressing system. The effects of 19TriTE on the proliferation and activation of T cells, as well as the specific cytotoxicity against CD19 positive tumor cell lines were verified. Read More

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TNFR2: Role in Cancer Immunology and Immunotherapy.

Immunotargets Ther 2021 21;10:103-122. Epub 2021 Apr 21.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, SAR, 999078, People's Republic of China.

Immune checkpoint inhibitors (ICIs), including anti-CTLA-4 (cytotoxic T lymphocyte antigen-4) and anti-PD-1/PD-L1 (programmed death-1/programmed death-ligand 1), represent a turning point in the cancer immunotherapy. However, only a minor fraction of patients could derive benefit from such therapy. Therefore, new strategies targeting additional immune regulatory mechanisms are urgently needed. Read More

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Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma.

Blood Adv 2021 Apr;5(8):2196-2215

Department of Hematology, Cancer Center Amsterdam, Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, The Netherlands.

Cell surface expression levels of GPRC5D, an orphan G protein-coupled receptor, are significantly higher on multiple myeloma (MM) cells, compared with normal plasma cells or other immune cells, which renders it a promising target for immunotherapeutic strategies. The novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, effectively kills GPRC5D+ MM cell lines in the presence of T cells from both healthy donors or heavily pretreated MM patients. In addition, talquetamab has potent anti-MM activity in bone marrow (BM) samples from 45 patients, including those with high-risk cytogenetic aberrations. Read More

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Applications of Macrocyclic Host Molecules in Immune Modulation and Therapeutic Delivery.

Front Chem 2021 6;9:658548. Epub 2021 Apr 6.

School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, United States.

The immune system plays a central role in the development and progression of human disease. Modulation of the immune response is therefore a critical therapeutic target that enables us to approach some of the most vexing problems in medicine today such as obesity, cancer, viral infection, and autoimmunity. Methods of manipulating the immune system through therapeutic delivery centralize around two common themes: the local delivery of biomaterials to affect the surrounding tissue or the systemic delivery of soluble material systems, often aided by context-specific cell or tissue targeting strategies. Read More

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Cervical Cancer Immunotherapy: Facts and Hopes.

Clin Cancer Res 2021 Apr 22. Epub 2021 Apr 22.

Department of Pathology, Johns Hopkins University

It is a sad fact that despite being almost completely preventable through human papillomavirus (HPV) vaccination and screening, cervical cancer remains the fourth most common cancer to affect women worldwide. Persistent high-risk HPV infection (hrHPV) is the primary etiological factor for cervical cancer. Upwards of 70% of cases are driven by HPV types 16 and 18, with a dozen other hrHPV associated with the remainder of cases. Read More

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Neurological complications of cancer immunotherapy.

Cancer Treat Rev 2021 Mar 23;97:102189. Epub 2021 Mar 23.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Austria.

Immunotherapy has emerged as a powerful therapeutic approach in many areas of clinical oncology and hematology. The approval of ipilimumab, a monoclonal antibody targeting the immune cell receptor CTLA-4, has marked the beginning of the era of immune checkpoint inhibitors. In the meantime, numerous antibodies targeting the PD-1 pathway have expanded the class of clinically approved immune checkpoint inhibitors. Read More

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License to kill: microsatellite instability and immune contexture.

Oncoimmunology 2021 Apr 2;10(1):1905935. Epub 2021 Apr 2.

Laboratory of Integrative Cancer Immunology, INSERM, Paris, France.

Colorectal cancers (CRCs) with microsatellite instability (MSI) are due to a defect in the DNA mismatch repair (MMR) system resulting in an accumulation of frame-shift mutations. They are characterized by a tumor microenvironment richer in cytotoxic CD8 T-cells (CTLs) and a better prognosis compared to microsatellite stable (MSS) CRCs. The mechanisms by which defective MMR system may influence tumor-infiltrating immune cells and their impact on patient survival were still unclear. Read More

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The immune response to SARS-CoV-2 and COVID-19 immunopathology - Current perspectives.

Pulmonology 2021 Apr 9. Epub 2021 Apr 9.

Basic and Clinical Immunology Unit, Department of Pathology, Faculty of Medicine, University of Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Portugal.

SARS-CoV-2 is a new beta coronavirus, similar to SARS-CoV-1, that emerged at the end of 2019 in the Hubei province of China. It is responsible for coronavirus disease 2019 (COVID-19), which was declared a pandemic by the World Health Organization on March 11, 2020. The ability to gain quick control of the pandemic has been hampered by a lack of detailed knowledge about SARS-CoV-2-host interactions, mainly in relation to viral biology and host immune response. Read More

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Orphan nuclear receptor TLX promotes immunosuppression via its transcriptional activation of PD-L1 in glioma.

J Immunother Cancer 2021 Apr;9(4)

Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China

Background: High-grade gliomas are rapidly progressing tumors of the central nervous system, and are associated with poor prognosis and highly immunosuppressive microenvironments. Meanwhile, a better understanding of PD-L1, a major prognostic biomarker for checkpoint immune therapy, regulation may provide insights for developing novel immunotherapeutic strategies for treating gliomas. In the present study, we elucidate the functional significance of the orphan nuclear receptor TLX in human glioma, and its functional role in immune suppression through regulation of PD-L1/PD-1 axis. Read More

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Highly efficient CRISPR-Cas9-mediated gene knockout in primary human B cells for functional genetic studies of Epstein-Barr virus infection.

PLoS Pathog 2021 Apr 15;17(4):e1009117. Epub 2021 Apr 15.

Research Unit Gene Vectors, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.

Gene editing is now routine in all prokaryotic and metazoan cells but has not received much attention in immune cells when the CRISPR-Cas9 technology was introduced in the field of mammalian cell biology less than ten years ago. This versatile technology has been successfully adapted for gene modifications in human myeloid cells and T cells, among others, but applications to human primary B cells have been scarce and limited to activated B cells. This limitation has precluded conclusive studies into cell activation, differentiation or cell cycle control in this cell type. Read More

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Switchable CAR-T Cells Outperformed Traditional Antibody-Redirected Therapeutics Targeting Breast Cancers.

ACS Synth Biol 2021 Apr 15. Epub 2021 Apr 15.

California Institute for Biomedical Research, 11119 North Torrey Pines Road, La Jolla, California 92037, United States.

Various antibody-redirected immunotherapeutic approaches, including antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), and chimeric antigen receptor-T (CAR-T) cells, have been devised to produce specific activity against various cancer types. Using genetically encoded unnatural amino acids, we generated a homogeneous Her2-targeted ADC, a T cell-redirected bsAb, and a FITC-modified antibody capable of redirecting anti-FITC CAR-T (switchable CAR-T; sCAR-T) cells to target different Her2-expressing breast cancers. sCAR-T cells showed activity against Her2-expressing tumor cells comparable to that of conventional anti-Her2 CAR-T cells and superior to that of ADC- and bsAb-based approaches. Read More

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Bacteria-Based Cancer Immunotherapy.

Adv Sci (Weinh) 2021 04 10;8(7):2003572. Epub 2021 Feb 10.

Key Laboratory of Advanced Technologies of Materials Ministry of Education School of Materials Science and Engineering Southwest Jiaotong University Chengdu 610031 China.

In the past decade, bacteria-based cancer immunotherapy has attracted much attention in the academic circle due to its unique mechanism and abundant applications in triggering the host anti-tumor immunity. One advantage of bacteria lies in their capability in targeting tumors and preferentially colonizing the core area of the tumor. Because bacteria are abundant in pathogen-associated molecular patterns that can effectively activate the immune cells even in the tumor immunosuppressive microenvironment, they are capable of enhancing the specific immune recognition and elimination of tumor cells. Read More

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Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies.

Oncoimmunology 2021 Mar 29;10(1):1900508. Epub 2021 Mar 29.

Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

Tertiary lymphoid structures (TLS) are ectopic cellular aggregates that resemble secondary lymphoid organs in their composition and structural organization. In contrast to secondary lymphoid organs, TLS are not imprinted during embryogenesis but are formed in non-lymphoid tissues in response to local inflammation. TLS structures exhibiting a variable degree of maturation are found in solid tumors. Read More

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Structural Basis of VSIG3: The Ligand for VISTA.

Front Immunol 2021 25;12:625808. Epub 2021 Mar 25.

New Drug Screening Center, China Pharmaceutical University, Nanjing, China.

B7 family members and their receptors play key roles in regulating T cell responses, and constitute very attractive targets for developing immunotherapeutic drugs. V-Set and Immunoglobulin domain containing 3 (VSIG3), a ligand for the novel B7 family immune checkpoint V-domain immunoglobulin suppressor of T cell activation (VISTA), can significantly inhibit T cell functions. Inhibitors targeting the VISTA/VSIG3 pathway are of great significance in tumor immunology. Read More

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Small-Molecule Natural Product Physachenolide C Potentiates Immunotherapy Efficacy by Targeting BET Proteins.

Cancer Res 2021 Apr 9. Epub 2021 Apr 9.

Basic Science Program, Frederick National Laboratory for Cancer Research.

Screening for sensitizers of cancer cells to TRAIL-mediated apoptosis identified a natural product (NP) of the 17β-hydroxywithanolide (17-BHW) class, physachenolide C (PCC), as a promising hit. In this study, we show that PCC was also able to sensitize melanoma and renal carcinoma cells to apoptosis in response not only to TRAIL, but also to the synthetic polynucleotide poly I:C, a viral mimetic and immune activator, by reducing levels of anti-apoptotic proteins cFLIP and Livin. Both death receptor and TLR3 signaling elicited subsequent increased assembly of a pro-apoptotic ripoptosome signaling complex. Read More

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Oncolytic herpesvirus expressing PD-L1 BiTE for cancer therapy: exploiting tumor immune suppression as an opportunity for targeted immunotherapy.

J Immunother Cancer 2021 Mar;9(4)

Department of Oncology, University of Oxford, Oxford, Oxfordshire, UK

Background: Programmed death-ligand 1 (PD-L1) is an important immune checkpoint protein that can be regarded as a pan-cancer antigen expressed by multiple different cell types within the tumor. While antagonizing PD-L1 is well known to relieve PD-1/PD-L1-mediated T cell suppression, here we have combined this approach with an immunotherapy strategy to target T cell cytotoxicity directly toward PD-L1-expressing cells. We developed a bi-specific T cell engager (BiTE) crosslinking PD-L1 and CD3ε and demonstrated targeted cytotoxicity using a clinically relevant patient-derived ascites model. Read More

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Polysaccharide-based nanomedicines for cancer immunotherapy: A review.

Bioact Mater 2021 Oct 18;6(10):3358-3382. Epub 2021 Mar 18.

Huaxi MR Research Center (HMRRC), Department of Radiology, Department of Neurosurgery, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China.

Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics. However, direct administration of "naked" immunotherapeutic agents (such as nucleic acids, cytokines, adjuvants or antigens without delivery vehicles) often results in: (1) an unsatisfactory efficacy due to suboptimal pharmacokinetics; (2) strong toxic and side effects due to low targeting (or off-target) efficiency. To overcome these shortcomings, a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects. Read More

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October 2021

Surface expression of the immunotherapeutic target G in osteosarcoma depends on cell confluency.

Cancer Rep (Hoboken) 2021 Apr 2:e1394. Epub 2021 Apr 2.

Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.

Background: Chimeric antigen receptor (CAR) T-cell therapy of pediatric sarcomas is challenged by the paucity of targetable cell surface antigens. A candidate target in osteosarcoma (OS) is the ganglioside G , but heterogeneous expression of G limits its value.

Aim: We aimed to identify mechanisms that upregulate G target expression in OS. Read More

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Specific Patterns of Blood ILCs in Metastatic Melanoma Patients and Their Modulations in Response to Immunotherapy.

Cancers (Basel) 2021 Mar 22;13(6). Epub 2021 Mar 22.

INSERM UMRS1160, Institut de Recherche Saint Louis, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.

Immunotherapy targeting immune checkpoint receptors brought a breakthrough in the treatment of metastatic melanoma patients. However, a number of patients still resist these immunotherapies. Present on CD8T cells, immune checkpoint receptors are expressed by innate lymphoid cells (ILCs), which may contribute to the clinical response. Read More

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The Role of Cytokines and Chemokines in Shaping the Immune Microenvironment of Glioblastoma: Implications for Immunotherapy.

Cells 2021 Mar 9;10(3). Epub 2021 Mar 9.

Translational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5001, Australia.

Glioblastoma is the most common form of primary brain tumour in adults. For more than a decade, conventional treatment has produced a relatively modest improvement in the overall survival of glioblastoma patients. The immunosuppressive mechanisms employed by neoplastic and non-neoplastic cells within the tumour can limit treatment efficacy, and this can include the secretion of immunosuppressive cytokines and chemokines. Read More

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Challenging Hurdles of Current Targeting in Glioblastoma: A Focus on Immunotherapeutic Strategies.

Int J Mol Sci 2021 Mar 28;22(7). Epub 2021 Mar 28.

Department of Oncology, University Hospital of Geneva, 1205 Geneva, Switzerland.

Glioblastoma is the most frequent primary neoplasm of the central nervous system and still suffers from very poor therapeutic impact. No clear improvements over current standard of care have been made in the last decade. For other cancers, but also for brain metastasis, which harbors a very distinct biology from glioblastoma, immunotherapy has already proven its efficacy. Read More

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CRISPR-Cas9-Mediated TIM3 Knockout in Human Natural Killer Cells Enhances Growth Inhibitory Effects on Human Glioma Cells.

Int J Mol Sci 2021 Mar 28;22(7). Epub 2021 Mar 28.

Department of Neurosurgery, Nara Medical University, Kashihara, Nara 634-8521, Japan.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Natural Killer (NK) cells are potent cytotoxic effector cells against tumor cells inducing GBM cells; therefore, NK cell based- immunotherapy might be a promising target in GBM. T cell immunoglobulin mucin family member 3 (TIM3), a receptor expressed on NK cells, has been suggested as a marker of dysfunctional NK cells. Read More

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Role of ADAM10 and ADAM17 in Regulating CD137 Function.

Int J Mol Sci 2021 Mar 8;22(5). Epub 2021 Mar 8.

Department of Dermatology, University of Kiel, 24105 Kiel, Germany.

Human CD137 (4-1BB), a member of the TNF receptor family, and its ligand CD137L (4-1BBL), are expressed on immune cells and tumor cells. CD137/CD137L interaction mediates bidirectional cellular responses of potential relevance in inflammatory diseases, autoimmunity and oncology. A soluble form of CD137 exists, elevated levels of which have been reported in patients with rheumatoid arthritis and various malignancies. Read More

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Nanotechnology synergized immunoengineering for cancer.

Eur J Pharm Biopharm 2021 Jun 24;163:72-101. Epub 2021 Mar 24.

Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA. Electronic address:

Novel strategies modulating the immune system yielded enhanced anticancer responses and improved cancer survival. Nevertheless, the success rate of immunotherapy in cancer treatment has been below expectation(s) due to unpredictable efficacy and off-target effects from systemic dosing of immunotherapeutic(s). As a result, there is an unmet clinical need for improving conventional immunotherapy. Read More

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The clinical efficacy of Rituximab administration in autoimmunity disorders, primary immunodeficiency diseases and malignancies.

Int Immunopharmacol 2021 Jun 24;95:107565. Epub 2021 Mar 24.

Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj 3149779453, Iran. Electronic address:

Rituximab (RTX), as a monoclonal antibody-based immunotherapeutic intervention targeting CD20 on B cells, has proven efficacy in the treatment of patients with some immune-mediated diseases. In the present review, we provided information on the immunobiological mechanisms of signaling for RTX and its clinical applications, according to the immune-pathophysiology involved in the microenvironment of multiple diseases. We highlighted combination therapy, dose schedules, and laboratory monitoring, as well as the associated common and rare side effects to avoid. Read More

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Phenotypic and Functional Analyses Guiding Combination Immune Checkpoint Immunotherapeutic Strategies in HTLV-1 Infection.

Front Immunol 2021 9;12:608890. Epub 2021 Mar 9.

Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) develops in 1-5% of HTLV-1-infected individuals. Previous studies by us and others have shown that the expression of negative immune checkpoint receptors (NCRs) is significantly increased on CD8 T cells in various chronic viral infections and are associated with poor anti-viral immunity. We have previously identified the differential expression of NCRs on CD8 T cells in blood from patients with HAM/TSP and in central nervous system (CNS) tissues of HTLV-1 infected humanized mice and defined the association with neurological complications. Read More

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