20,896 results match your criteria receptor tcr

Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'.

Nat Commun 2021 07 26;12(1):4515. Epub 2021 Jul 26.

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.

The in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we use single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. Read More

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NR4A3 Mediates Thymic Negative Selection.

J Immunol 2021 Jul 26. Epub 2021 Jul 26.

Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada;

Central tolerance aims to limit the production of T lymphocytes bearing TCR with high affinity for self-peptide presented by MHC molecules. The accumulation of thymocytes with such receptors is limited by negative selection or by diversion into alternative differentiation, including T regulatory cell commitment. A role for the orphan nuclear receptor NR4A3 in negative selection has been suggested, but its function in this process has never been investigated. Read More

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Fibroblast growth factor receptor 3 alterations and response to immune checkpoint inhibition in metastatic urothelial cancer: a real world experience.

Br J Cancer 2021 Jul 22. Epub 2021 Jul 22.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Background: FGFR3-altered urothelial cancer (UC) correlates with a non-T cell-inflamed phenotype and has therefore been postulated to be less responsive to immune checkpoint blockade (ICB). Preclinical work suggests FGFR3 signalling may suppress pathways such as interferon signalling that alter immune microenvironment composition. However, correlative studies examining clinical trials have been conflicting as to whether FGFR altered tumours have equivalent response and survival to ICB in patients with metastatic UC. Read More

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A CVID-associated variant in the ciliogenesis protein CCDC28B disrupts immune synapse assembly.

Cell Death Differ 2021 Jul 22. Epub 2021 Jul 22.

Department of Life Sciences, University of Siena, Siena, Italy.

Ciliogenesis proteins orchestrate vesicular trafficking pathways that regulate immune synapse (IS) assembly in the non-ciliated T-cells. We hypothesized that ciliogenesis-related genes might be disease candidates for common variable immunodeficiency with impaired T-cell function (T-CVID). We identified a heterozygous, predicted pathogenic variant in the ciliogenesis protein CCDC28B present with increased frequency in a large CVID cohort. Read More

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Deep Sequencing of T-Cell Receptors for Monitoring Peripheral CD8 T Cells in Chinese Advanced Non-Small-Cell Lung Cancer Patients Treated With the Anti-PD-L1 Antibody.

Front Mol Biosci 2021 9;8:679130. Epub 2021 Jul 9.

Department of Medical Oncology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.

Atezolizumab, a high-affinity engineered human anti-PD-L1 antibody, has produced a clinical benefit for patients with advanced non-small-cell lung cancer (NSCLC). However, associated with T-cell regulation, the immunomodulatory effect of PD-L1 blockade and its biomarker in peripheral immunity remains elusive. In a prospective cohort with 12 Chinese advanced NSCLC patients who received atezolizumab 1,200 mg every 3 weeks as a second-line treatment, blood samples were obtained before and 6 weeks after atezolizumab initiation, and when disease progression was confirmed. Read More

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On the border of the amyloidogenic sequences: prefix analysis of the parallel beta sheets in the PDB_Amyloid collection.

J Integr Bioinform 2021 Jul 26. Epub 2021 Jul 26.

PIT Bioinformatics Group, Eötvös University, BudapestH-1117, Hungary.

The Protein Data Bank (PDB) today contains more than 174,000 entries with the 3-dimensional structures of biological macromolecules. Using the rich resources of this repository, it is possible identifying subsets with specific, interesting properties for different applications. Our research group prepared an automatically updated list of amyloid- and probably amyloidogenic molecules, the PDB_Amyloid collection, which is freely available at the address http://pitgroup. Read More

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Simultaneous monitoring assay for T-cell receptor stimulation-dependent activation of CD4 and CD8 T cells using inducible markers on the cell surface.

Biochem Biophys Res Commun 2021 Jul 21;571:53-59. Epub 2021 Jul 21.

Laboratory of Immunosenescence, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan. Electronic address:

Isolation of antigen (Ag)-specific T cells is an important step in the investigation of T-cell immunity. Activation-induced markers (AIMs), such as CD154/tumor necrosis factor (TNF)/CD107A/CD134/CD137 enable the sorting of Ag-specific T cells without using human leukocyte antigen (HLA)-multimers. However, optimal conditions suitable for simultaneous detection of both Ag-specific CD4 and CD8 T cells have not been investigated. Read More

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The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events.

Front Immunol 2021 6;12:703534. Epub 2021 Jul 6.

Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GCI3), Medical Faculty of the Otto-von-Guericke University, Magdeburg, Germany.

T cells are the key players of the adaptive immune response. They coordinate the activation of other immune cells and kill malignant and virus-infected cells. For full activation T cells require at least two signals. Read More

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Quantitative assessment of HER2 gene amplification of breast cancer using droplet digital PCR.

Pathol Int 2021 Jul 21. Epub 2021 Jul 21.

Department of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

We previously reported the usefulness of droplet digital polymerase chain reaction (ddPCR) for the assessment of Human epithelial growth factor receptor 2 (HER2) gene amplification in breast cancer using formalin-fixed and paraffin-embedded sections. In our previous study, we combined HER2/CEP17 ratio (HER2 gene signals to chromosome 17 signals) with ddPCR and tumor content ratio (TCR) of each sample and determined the HER2 status by adopting a two-dimensional chart. This "ddPCR-TCR method" showed a high concordance with conventional HER2 status. Read More

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Combining Well-Tempered Metadynamics Simulation and SPR Assays to Characterize the Binding Mechanism of the Universal T-Lymphocyte Tetanus Toxin Epitope TT830-843.

Biomed Res Int 2021 4;2021:5568980. Epub 2021 Jul 4.

Centro de Desenvolvimento Tecnológico em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Peptide TT830-843 from the tetanus toxin is a universal T-cell epitope. It helps in vaccination and induces T-cell activation. However, the fine molecular interaction between this antigen and the major histocompatibility complex (MHC) remains unknown. Read More

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Systemic inhibition of PTPN22 augments anticancer immunity.

J Clin Invest 2021 Jul 20. Epub 2021 Jul 20.

Sidney Kimmel Comprehensive Cancer Center, John Hopkins University, Baltimore, United States of America.

Both epidemiologic and cellular studies in the context of autoimmune diseases have established that protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a key regulator of T cell receptor (TCR) signaling. However, its mechanism of action in tumors and its translatability as a target for cancer immunotherapy have not been established. Here we show that a germline variant of PTPN22, rs2476601, portended a lower likelihood of cancer in patients. Read More

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High-throughput and single-cell T cell receptor sequencing technologies.

Nat Methods 2021 Jul 19. Epub 2021 Jul 19.

Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.

T cells express T cell receptors (TCRs) composed of somatically recombined TCRα and TCRβ chains, which mediate recognition of major histocompatibility complex (MHC)-antigen complexes and drive the antigen-specific adaptive immune response to pathogens and cancer. The TCR repertoire in each individual is highly diverse, which allows for recognition of a wide array of foreign antigens, but also presents a challenge in analyzing this response using conventional methods. Recent studies have developed high-throughput sequencing technologies to identify TCR sequences, analyze their antigen specificities using experimental and computational tools, and pair TCRs with transcriptional and epigenetic cell state phenotypes in single cells. Read More

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Multi-scale simulations of the T cell receptor reveal its lipid interactions, dynamics and the arrangement of its cytoplasmic region.

PLoS Comput Biol 2021 Jul 19;17(7):e1009232. Epub 2021 Jul 19.

Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom.

The T cell receptor (TCR-CD3) initiates T cell activation by binding to peptides of Major Histocompatibility Complexes (pMHC). The TCR-CD3 topology is well understood but the arrangement and dynamics of its cytoplasmic tails remains unknown, limiting our grasp of the signalling mechanism. Here, we use molecular dynamics simulations and modelling to investigate the entire TCR-CD3 embedded in a model membrane. Read More

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LFA-1 and Kindlin-3 enable the collaborative transport of SLP-76 microclusters by myosin and dynein motors.

J Cell Sci 2021 Jul 19. Epub 2021 Jul 19.

Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA.

Integrin engagement within the immune synapse enhances T cell activation, but our understanding of this process is incomplete. In response to T cell receptor (TCR) ligation, SLP-76 (LCP2), ADAP (FYB), and SKAP-55 (SKAP1) are recruited into microclusters and activate integrins via the effectors Talin-1 and Kindlin-3. We postulated that integrins influence the centripetal transport and signaling of SLP-76 microclusters via these linkages. Read More

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Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development.

Front Genet 2021 2;12:679616. Epub 2021 Jul 2.

Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China.

Intrathymic differentiation of T lymphocytes begins as early as intrauterine stage, yet the T cell lineage decisions of human fetal thymocytes at different gestational ages are not currently understood. Here, we performed integrative single-cell analyses of thymocytes across gestational ages. We identified conserved candidates underlying the selection of T cell receptor (TCR) lineages in different human fetal stages. Read More

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Pharmacological MEK inhibition promotes polyclonal T-cell reconstitution and suppresses xenogeneic GVHD.

Cell Immunol 2021 Jul 13;367:104410. Epub 2021 Jul 13.

Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.

Rapid immune reconstitution without developing graft-versus-host disease (GVHD) is required for the success of allogeneic hematopoietic stem cell transplantation. Here, we analyzed the effects of pharmacological MEK inhibition on human polyclonal T-cell reconstitution in a humanized mouse GVHD model utilizing deep sequencing-based T-cell receptor (TCR) repertoire analysis. GVHD mice exhibited a skewed TCR repertoire with a common clone within target organs. Read More

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CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor.

Proc Natl Acad Sci U S A 2021 Jul;118(29)

Faculty of Health Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom;

CD8 T cells are inherently cross-reactive and recognize numerous peptide antigens in the context of a given major histocompatibility complex class I (MHCI) molecule via the clonotypically expressed T cell receptor (TCR). The lineally expressed coreceptor CD8 interacts coordinately with MHCI at a distinct and largely invariant site to slow the TCR/peptide-MHCI (pMHCI) dissociation rate and enhance antigen sensitivity. However, this biological effect is not necessarily uniform, and theoretical models suggest that antigen sensitivity can be modulated in a differential manner by CD8. Read More

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The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy.

Front Oncol 2021 29;11:641428. Epub 2021 Jun 29.

Department of Life & Consumer Sciences, University of South Africa, Johannesburg, South Africa.

Through genetic and epigenetic alterations, cancer cells present the immune system with a diversity of antigens or neoantigens, which the organism must distinguish from self. The immune system responds to neoantigens by activating naïve T cells, which mount an anticancer cytotoxic response. T cell activation begins when the T cell receptor (TCR) interacts with the antigen, which is displayed by the major histocompatibility complex (MHC) on antigen-presenting cells (APCs). Read More

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Drug and Chemical Allergy: A Role for a Specific Naive T-Cell Repertoire?

Front Immunol 2021 29;12:653102. Epub 2021 Jun 29.

Inflammation, Microbiome and Immunosurveillance, Université Paris-Saclay, INSERM, Châtenay-Malabry, France.

Allergic reactions to drugs and chemicals are mediated by an adaptive immune response involving specific T cells. During thymic selection, T cells that have not yet encountered their cognate antigen are considered naive T cells. Due to the artificial nature of drug/chemical-T-cell epitopes, it is not clear whether thymic selection of drug/chemical-specific T cells is a common phenomenon or remains limited to few donors or simply does not exist, suggesting T-cell receptor (TCR) cross-reactivity with other antigens. Read More

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Central Nervous System-Infiltrating T Lymphocytes in Stroke Are Activated via Their TCR (T-Cell Receptor) but Lack CD25 Expression.

Stroke 2021 Jul 16:STROKEAHA120032763. Epub 2021 Jul 16.

Department of Neurology, University Medicine, Greifswald, Germany. (J.S., J.G., A.V.).

Background And Purpose: T lymphocytes contribute to secondary brain damage after stroke. It has not been fully investigated whether this contribution is caused by antigen-specific or antigen-nonspecific activation of T lymphocytes. Lymphocytes from Nur77 transgenic mice express a fluorescent protein upon activation via the TCR (T-cell receptor), allowing the differentiation of activation mode in a natural repertoire of immune cells and antigens. Read More

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Mapping T Cell Responses to Native and Neo-Islet Antigen Epitopes in at Risk and Type 1 Diabetes Subjects.

Front Immunol 2021 25;12:675746. Epub 2021 Jun 25.

Department of Immunobiology, King's College London, Guy's Hospital, London, United Kingdom.

Aims: Recent studies highlight the potentially important role of neoepitopes in breaking immune tolerance in type 1 diabetes. T cell reactivity to these neoepitopes has been reported, but how this response compares quantitatively and phenotypically with previous reports on native epitopes is not known. Thus, an understanding of the relationship between native and neoepitopes and their role as tolerance breakers or disease drivers in type 1 diabetes is required. Read More

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New insights into TCR β-selection.

Trends Immunol 2021 Jul 12. Epub 2021 Jul 12.

Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address:

T cell receptor (TCR) β-selection (herein referred to as β-selection) is a pivotal checkpoint in mammalian T cell development when immature CD4CD8 T-cells (thymocytes) express pre-TCR following successful Tcrb gene rearrangement. At this stage, αβ T cell lineage commitment and allelic exclusion to restrict one β-chain per cell take place and thymocytes undergo a proliferative burst. β-selection is known to be crucially dependent upon synchronized Notch and pre-TCR signaling; however, other necessary inputs have been identified over the past decade, expanding our knowledge and understanding of the β-selection process. Read More

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Zearalenone and deoxynivalenol reduced Th1-mediated cellular immune response after Listeria monocytogenes infection by inhibiting CD4 T cell activation and differentiation.

Environ Pollut 2021 Sep 5;284:117514. Epub 2021 Jun 5.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, China. Electronic address:

Based on the fact that mycotoxins and the food-borne bacteria coexist in the natural environment and pose a significant health hazard to humans and animals, it is important to investigate the immunosuppressive mechanism of ZEA (zearalenone), DON (deoxynivalenol), and their combination in bacterial infections. In this study, we established a mouse model of mycotoxin low-dose exposure combined with Listeria monocytogenes infection and investigated the effects of ZEA, DON and their combination on Th1-mediated anti-intracellular bacterial infection based on CD4 T cell activation and differentiation using both in vitro and in vivo analyses. The present study showed that both ZEA and DON aggravated Listeria monocytogenes infection in mice and affected the activation of CD4 T cells and Th1 differentiation, including the effects on costimulatory molecules CD28 and CD152 and on cross-linking of IL-12 and IL-12R, by inhibiting T cell receptor (TCR) signaling. Read More

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September 2021

Allosteric activation of T cell antigen receptor signaling by quaternary structure relaxation.

Cell Rep 2021 Jul;36(2):109375

T-cell signalling laboratory, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK. Electronic address:

The mechanism of T cell antigen receptor (TCR-CD3) signaling remains elusive. Here, we identify mutations in the transmembrane region of TCRβ or CD3ζ that augment peptide T cell antigen receptor (pMHC)-induced signaling not explicable by enhanced ligand binding, lateral diffusion, clustering, or co-receptor function. Using a biochemical assay and molecular dynamics simulation, we demonstrate that the gain-of-function mutations loosen the interaction between TCRαβ and CD3ζ. Read More

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Dupilumab as a therapy option for treatment refractory mogamulizumab-associated rash.

JAAD Case Rep 2021 Aug 9;14:37-42. Epub 2021 Jun 9.

Division of Dermatology, Beckman Research Institute, City of Hope Medical Center, Duarte, California.

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Diversity and shared T-cell receptor repertoire analysis in esophageal squamous cell carcinoma.

Oncol Lett 2021 Aug 24;22(2):618. Epub 2021 Jun 24.

Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

The tumor immune response is dependent on the interaction between tumor cells and the T-cell subset expressing the T-cell receptor (TCR) repertoire that infiltrates into the tumor microenvironment. The present study explored the diversity and shared TCR repertoires expressed on the surface of locoregional T cells and identified the T lymphocyte subsets infiltrating into esophageal squamous cell carcinoma (ESCC), in order to provide insight into the efficiency of immunotherapy and the development of a novel immune-oriented therapeutic strategy. A total of 53 patients with ESCC were enrolled in the present study, and immunohistochemical analysis of CD3, CD8, CD45RO, FOXP3, CD274, HLA class I and AE1/AE3 was performed. Read More

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Interferon-α-producing plasmacytoid dendritic cells drive the loss of adipose tissue regulatory T cells during obesity.

Cell Metab 2021 Jul 8. Epub 2021 Jul 8.

Department of Immunology, Harvard Medical School, Boston, MA, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address:

The visceral adipose tissue (VAT) of lean mice hosts a unique population of regulatory T cells (Tregs) that have a distinct transcriptome and T cell receptor (TCR) repertoire and regulate local and systemic inflammation and metabolism. Perplexingly, this population disappears in obese mice, limiting the promise of Treg-based therapies for metabolic disorders. We exploited the power of a VAT-Treg TCR-transgenic mouse model to follow the dynamics of, and phenotypic changes in, the VAT-Treg population throughout the development of diet-induced obesity. Read More

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Effector Vγ9Vδ2 T cell response to congenital Toxoplasma gondii infection.

JCI Insight 2021 Jul 13. Epub 2021 Jul 13.

Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.

A major γδ T cell population in human adult blood are the Vγ9Vδ2 T cells that are activated and expanded in a T cell receptor (TCR)-dependent manner by microbe- and endogenous-derived phosphorylated prenyl metabolites (phosphoantigens). Vγ9Vδ2 T cells are also abundant in human fetal peripheral blood, but compared to their adult counterparts they have a distinct developmental origin, are hyporesponsive towards in vitro phosphoantigen exposure and they do not possess a cytotoxic effector phenotype. In order to obtain insight into the role of Vγ9Vδ2 T cells in the human fetus, we investigated their response to in utero infection with the phosphoantigen-producing parasite Toxoplasma gondii (T. Read More

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Deep learning identifies antigenic determinants of severe SARS-CoV-2 infection within T-cell repertoires.

Sci Rep 2021 07 12;11(1):14275. Epub 2021 Jul 12.

Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

SARS-CoV-2 infection is characterized by a highly variable clinical course with patients experiencing asymptomatic infection all the way to requiring critical care support. This variation in clinical course has led physicians and scientists to study factors that may predispose certain individuals to more severe clinical presentations in hopes of either identifying these individuals early in their illness or improving their medical management. We sought to understand immunogenomic differences that may result in varied clinical outcomes through analysis of T-cell receptor sequencing (TCR-Seq) data in the open access ImmuneCODE database. Read More

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Single-cell RNA sequencing reveals distinct cellular factors for response to immunotherapy targeting CD73 and PD-1 in colorectal cancer.

J Immunother Cancer 2021 Jul;9(7)

Therapeutics & Biotechnology Division, Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea

Background: Although cancer immunotherapy is one of the most effective advanced-stage cancer therapies, no clinically approved cancer immunotherapies currently exist for colorectal cancer (CRC). Recently, programmed cell death protein 1 (PD-1) blockade has exhibited clinical benefits according to ongoing clinical trials. However, ongoing clinical trials for cancer immunotherapies are focused on PD-1 signaling inhibitors such as pembrolizumab, nivolumab, and atezolizumab. Read More

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