Search Our Scientific Publications & Authors

J Immunol 2021 Apr 15. Epub 2021 Apr 15.

Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic;

Ag-inexperienced memory-like T (AIMT) cells are functionally unique T cells, representing one of the two largest subsets of murine CD8 T cells. However, differences between laboratory inbred strains, insufficient data from germ-free mice, a complete lack of data from feral mice, and an unclear relationship between AIMT cells formation during aging represent major barriers for better understanding of their biology. We performed a thorough characterization of AIMT cells from mice of different genetic background, age, and hygienic status by flow cytometry and multiomics approaches, including analyses of gene expression, TCR repertoire, and microbial colonization. Read More

J Leukoc Biol 2021 Apr 13. Epub 2021 Apr 13.

Department of Immunology, Laboratory Medical Immunology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T lymphocyte response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to disease course severity. Read More

J Invest Dermatol 2021 Apr 9. Epub 2021 Apr 9.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address:

In psoriasis, CD8CD103 memory T cells residing in the epidermis represent an effector population capable of maintaining the condition and driving a recurrence of the disease. Tissue-infiltrating CD8 T cells expressing programmed cell death protein-1 (PD-1) are regarded as antigen-primed effector cells in others chronic inflammatory diseases. However, the expression and significance of PD-1 on skin-infiltrating CD8 T cells in human psoriasis is not known. Read More

Hum Vaccin Immunother 2021 Apr 6:1-8. Epub 2021 Apr 6.

Laboratory for Diagnosis of Clinical Microbiology and Infection, Yuebei People's Hospital, Shantou University Medical College, Shaoguan, China.

Cellular immunity is crucial for an efficient host immune response against rabies virus (RABV) infection. But the T cell receptor (TCR) repertoire in human after RABV vaccine immunization remained unclear. In this study, we conducted high-throughput sequencing of TCR β chain complementarity determining region 3(CDR3) repertoires in 4 healthy volunteers before and after immunization with RABV vaccine. Read More

FASEB J 2021 May;35(5):e21535

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Thymic epithelial cells (TECs) are indispensable for T cell development, T cell receptor (TCR) repertoire selection, and specific lineage differentiation. Medullary thymic epithelial cells (mTECs), which account for the majority of TECs in adults, are critical for thymocyte selection and self-tolerance. CD74 is a nonpolymorphic transmembrane glycoprotein of major histocompatibility complex class II (MHCII) that is expressed in TECs. Read More

Cells 2021 03 12;10(3). Epub 2021 Mar 12.

Department of Microbiology, Immunology & Genetics, University of North Texas Health Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global pandemic of coronavirus disease 2019 (COVID-19) and particularly exhibits severe symptoms and mortality in elderly individuals. Mounting evidence shows that the characteristics of the age-related clinical severity of COVID-19 are attributed to insufficient antiviral immune function and excessive self-damaging immune reaction, involving T cell immunity and associated with pre-existing basal inflammation in the elderly. Age-related changes to T cell immunosenescence is characterized by not only restricted T cell receptor (TCR) repertoire diversity, accumulation of exhausted and/or senescent memory T cells, but also by increased self-reactive T cell- and innate immune cell-induced chronic inflammation, and accumulated and functionally enhanced polyclonal regulatory T (Treg) cells. Read More

Oncoimmunology 2021 Mar 17;10(1):1899609. Epub 2021 Mar 17.

State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

An indicator for systemic evaluation of the adaptive immune status is lacking. Peripheral blood is important in antitumour immunity, and the T-cell receptor (TCR) repertoire diversity is key for effective immunity. This study aimed to investigate changes in the circulating T cell receptor β chain (TCRB) diversity during the first few (1 ~ 4) treatment cycles and its clinical value in patients with advanced lung cancer. Read More

medRxiv 2021 Mar 22. Epub 2021 Mar 22.

Measuring the adaptive immune response to SARS-CoV-2 can enable the assessment of past infection as well as protective immunity and the risk of reinfection. While neutralizing antibody (nAb) titers are one measure of protection, such assays are challenging to perform at a large scale and the longevity of the SARS-CoV-2 nAb response is not fully understood. Here, we apply a T-cell receptor (TCR) sequencing assay that can be performed on a small volume standard blood sample to assess the adaptive T-cell response to SARS-CoV-2 infection. Read More

Front Immunol 2021 15;12:626793. Epub 2021 Mar 15.

Roche Sequencing Solutions, Pleasanton, CA, United States.

It is increasingly clear that an extraordinarily diverse range of clinically important conditions-including infections, vaccinations, autoimmune diseases, transplants, transfusion reactions, aging, and cancers-leave telltale signatures in the millions of V(D)J-rearranged antibody and T cell receptor [TR per the Human Genome Organization (HUGO) nomenclature but more commonly known as TCR] genes collectively expressed by a person's B cells (antibodies) and T cells. We refer to these as the . Because of its diversity and complexity, the immunome provides singular opportunities for advancing personalized medicine by serving as the substrate for a highly multiplexed, near-universal blood test. Read More

Immunology 2021 Mar 31. Epub 2021 Mar 31.

Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA.

Age-related thymic atrophy results in reduced output of naïve conventional T (Tcon) cells. However, its impact on regulatory T (Treg) cells is insufficiently understood. Given evidence that thymic Treg (tTreg) cell generation is enhanced in the aged, atrophy thymus and that the aged periphery accumulates peripheral Treg (pTreg) cells, we asked why these Treg cells are unable to effectively attenuate increased autoreactivity-induced chronic inflammation in the elderly. Read More

Front Oncol 2021 11;11:537735. Epub 2021 Mar 11.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Lung cancer is the leading cause of cancer-related deaths worldwide, and its occurrence is related to the accumulation of gene mutations and immune escape of the tumor. Sequencing of the T-cell receptor (TCR) repertoire can reveal the immunosurveillance status of the tumor microenvironment, which is related to tumor escape and immunotherapy. This study aimed to determine the characteristics and clinical significance of the TCR repertoire in lung cancer. Read More

Front Immunol 2021 11;12:640725. Epub 2021 Mar 11.

La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.

The adaptive immune system in vertebrates has evolved to recognize non-self antigens, such as proteins expressed by infectious agents and mutated cancer cells. T cells play an important role in antigen recognition by expressing a diverse repertoire of antigen-specific receptors, which bind epitopes to mount targeted immune responses. Recent advances in high-throughput sequencing have enabled the routine generation of T-cell receptor (TCR) repertoire data. Read More

J Immunother Cancer 2021 Mar;9(3)

Medigene Immunotherapies GmbH, Planegg-Martinsried, Germany.

Background: The cancer-testis antigen MAGE-A4 is an attractive target for T-cell-based immunotherapy, especially for indications with unmet clinical need like non-small cell lung or triple-negative breast cancer.

Methods: An unbiased CD137-based sorting approach was first used to identify an immunogenic MAGE-A4-derived epitope (GVYDGREHTV) that was properly processed and presented on human leukocyte antigen (HLA)-A2 molecules encoded by the HLA-A*02:01 allele. To isolate high-avidity T cells via subsequent multimer sorting, an in vitro priming approach using HLA-A2-negative donors was conducted to bypass central tolerance to this self-antigen. Read More

BMC Bioinformatics 2021 Mar 25;22(1):159. Epub 2021 Mar 25.

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Background: Deep immune receptor sequencing, RepSeq, provides unprecedented opportunities for identifying and studying condition-associated T-cell clonotypes, represented by T-cell receptor (TCR) CDR3 sequences. However, due to the immense diversity of the immune repertoire, identification of condition relevant TCR CDR3s from total repertoires has mostly been limited to either "public" CDR3 sequences or to comparisons of CDR3 frequencies observed in a single individual. A methodology for the identification of condition-associated TCR CDR3s by direct population level comparison of RepSeq samples is currently lacking. Read More

Res Sq 2021 Mar 16. Epub 2021 Mar 16.

During the COVID-19 pandemic, thousands of pregnant women have been infected with SARS-CoV-2. The implications of maternal SARS-CoV-2 infection on fetal and childhood well-being are unknown. We aimed to characterize the fetal immune response to maternal SARS-CoV-2 infection. Read More

JCI Insight 2021 Mar 23. Epub 2021 Mar 23.

Division of Cancer Immunology, National Cancer Center, Kashiwa, Japan.

Patients with colorectal cancers (CRCs) generally exhibit improved survival through intensive lymph node (LN) dissection. However, recent progress in cancer immunotherapy revisits the potential importance of regional LNs, where T cells are primed to attack tumor cells. To elucidate the role of regional LN, we investigated the immunological status of non-metastatic regional LN lymphocytes (LNLs) in comparison with those in the tumor microenvironment (tumor-infiltrating lymphocytes; TILs) using flow cytometry and next-generation sequencing. Read More

Cancer Immunol Immunother 2021 Mar 9. Epub 2021 Mar 9.

Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, Japan.

Introduction: TCR and BCR repertoire diversity plays a critical role in tumor immunity. Thus, analysis of TCR and BCR repertoires might help predict the clinical efficacy of anti-PD-1 treatment.

Methods: Blood samples from 30 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1 antibody were collected before and six weeks after treatment initiation. Read More

Immunother Adv 2021 Jan 25;1(1):ltaa001. Epub 2020 Nov 25.

Centre for Cancer Immunology, School of Cancer Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, UK.

Objectives: Regulatory T cells (Treg) play a major role in the suppression of protective anti-tumour T cell responses. In the CT26 BALB/c murine model of colorectal carcinoma, Tregs differentially suppress responses to two characterised CD8+ T epitopes, AH1 and GSW11, which results in an absence of detectable IFN-γ-producing GSW11-specific T cells in the spleen and lymph nodes of tumour challenged mice. Activation of GSW11-specific T cells correlates with protection against tumour progression. Read More

Sci Adv 2021 03 19;7(12). Epub 2021 Mar 19.

Centre International de Recherche en Infectiologie (CIRI); INSERM, U1111; Université de Lyon 1; Ecole Normale Supérieure de Lyon; and CNRS, UMR 5308, Lyon, France.

Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous adverse drug reaction. To better understand why skin symptoms are so severe, we conducted a prospective immunophenotyping study on skin and blood. Mass cytometry results confirmed that effector memory polycytotoxic CD8 T cells (CTLs) are the main leucocytes in TEN blisters at the acute phase. Read More

Front Immunol 2021 24;12:640190. Epub 2021 Feb 24.

Cellular Immunology Section, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States.

The epidemic spread of Zika virus (ZIKV), associated with devastating neurologic syndromes, has driven the development of multiple ZIKV vaccines candidates. An effective vaccine should induce ZIKV-specific T cell responses, which are shown to improve the establishment of humoral immunity and contribute to viral clearance. Here we investigated how previous immunization against Japanese encephalitis virus (JEV) and yellow fever virus (YFV) influences T cell responses elicited by a Zika purified-inactivated virus (ZPIV) vaccine. Read More

Front Immunol 2021 25;12:618610. Epub 2021 Feb 25.

Research Department of Hematology, Cancer Institute, University College London, London, United Kingdom.

The benefit of autologous stem cell transplantation (ASCT) in newly diagnosed myeloma patients, apart from supporting high dose chemotherapy, may include effects on T cell function in the bone marrow (BM). We report our exploratory findings on marrow infiltrating T cells early post-ASCT (day+100), examining phenotype and T cell receptor (TCR) repertoire, seeking correlations with timing of relapse. Compared to healthy donors (HD), we observed an increase in regulatory T cells (CD4+FoxP3+, Tregs) with reduction in CD4 T cells, leading to lower CD4:8 ratios. Read More

Front Immunol 2021 24;12:614276. Epub 2021 Feb 24.

Quantitative and Systems Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.

The human immune system relies on the capability of CD8 T cells to patrol body cells, spot infected cells and eliminate them. This cytotoxic response is supposed to be limited to infected cells to avoid killing of healthy cells. To enable this, CD8 T cells have T Cell Receptors (TCRs) which should discriminate between self and non-self through the recognition of antigenic peptides bound to Human Leukocyte Antigen class I (HLA-I) complexes-i. Read More

Int J Radiat Oncol Biol Phys 2021 Mar 10. Epub 2021 Mar 10.

Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Purpose: This work assessed local and systemic alternations of the tumor immune microenvironment (TIME) during concurrent chemoradiotherapy (CCRT) of local advanced cervical cancer to estimate the optimal timing for immune therapy in relation to CCRT.

Methods: In this single-center prospective clinical trial, 55 patients with stage IIA-IVA cervical cancer were enrolled between December 2016 and November 2017. The median follow-up was 32. Read More

Trends Pharmacol Sci 2021 Apr;42(4):268-282

Center for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Cancer transcriptomes frequently exhibit RNA dysregulation. As the resulting aberrant transcripts may be translated into cancer-specific proteins, there is growing interest in exploiting RNA dysregulation as a source of tumor antigens (TAs) and thus novel immunotherapy targets. Recent advances in high-throughput technologies and rapid accumulation of multiomic cancer profiling data in public repositories have provided opportunities to systematically characterize RNA dysregulation in cancer and identify antigen targets for immunotherapy. Read More

Front Immunol 2021 23;12:599133. Epub 2021 Feb 23.

Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.

Sixteen monozygotic cystic fibrosis (CF) twin pairs of whom 14 pairs were homozygous for the most common p.Phe508del mutation were selected from the European Cystic Fibrosis Twin and Sibling Study Cohort. The monozygotic twins were examined in their T cell receptor (TCR) repertoire in peripheral blood by amplicon sequencing of the CDR3 variable region of the ß-chain. Read More

J Clin Invest 2021 Mar 11. Epub 2021 Mar 11.

Cedars-Sinai Medical Center, Los Angeles, United States of America.

Multisystem Inflammatory Syndrome in Children (MIS-C), a hyperinflammatory syndrome associated with SARS-CoV-2 infection, shares clinical features with toxic shock syndrome, which is triggered by bacterial superantigens. Superantigen specificity for different Vβ-chains results in Vβ-skewing, whereby T cells with specific Vβ-chains and diverse antigen specificity are overrepresented in the TCR repertoire. Here, we characterized the TCR repertoire of MIS-C patients and found a profound expansion of TCR Βeta Variable gene (TRBV)11-2, with up to 24% of clonal T cell space occupied by TRBV11-2 T cells, which correlated with MIS-C severity and serum cytokine levels. Read More

Front Immunol 2021 22;12:610149. Epub 2021 Feb 22.

Institute of Cancer, Xinqiao Hospital, Army Medical University, Chongqing, China.

Breast cancer is one of the most commonly diagnosed malignancies. Although endocrine therapy improves the survival of patients with hormone receptor (HR)-positive breast cancer, the post-endocrine therapy strategy for metastatic breast cancer remains challenging. Herein, we report two patients who benefited from antiestrogen agents combined with an immunotherapy regimen to support the notion that an immunotherapy combination regimen may be a potential treatment for patients with HR-positive metastatic breast cancer post-endocrine therapy. Read More

Immunity 2021 Mar;54(3):586-602.e8

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. Electronic address:

To identify disease-relevant T cell receptors (TCRs) with shared antigen specificity, we analyzed 778,938 TCRβ chain sequences from 178 non-small cell lung cancer patients using the GLIPH2 (grouping of lymphocyte interactions with paratope hotspots 2) algorithm. We identified over 66,000 shared specificity groups, of which 435 were clonally expanded and enriched in tumors compared to adjacent lung. The antigenic epitopes of one such tumor-enriched specificity group were identified using a yeast peptide-HLA A02:01 display library. Read More

J Cell Mol Med 2021 Apr 8;25(8):3991-4000. Epub 2021 Mar 8.

Department of Gastroenterology, Nanjing University Medical School Affiliated Drum Tower Hospital, Nanjing, China.

Pancreatic cancer (PC) has been the fourth cancer-related death worldwide, diagnosed at an unresectable stage due to its rapid progression and few symptoms of this disease at early stages. The aim of this study was to determine the association between the diversity of T-cell receptor (TCR) repertoire and clinicopathological characteristics of patients with PC and other benign pancreatic diseases. In order to make a comprehensive analysis the TCR repertoire, high-throughput sequencing was used to differentiate complementarity determining region 3 (CDR3) of the TCR β chain in peripheral blood samples from 3 PC, 3 chronic pancreatitis, 3 pancreatic cystic lesions and 3 pancreatic neuroendocrine tumour patients. Read More

Front Immunol 2021 18;12:595355. Epub 2021 Feb 18.

Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China.

To study the characteristics of the T cell receptor (TCR) repertoire in cancer tissue, peripheral blood and regional lymph nodes (LNs) from patients with papillary thyroid carcinoma (PTC). PTC tissue, peripheral blood mononuclear cells (PBMCs) and regional LNs of six patients with papillary thyroid carcinoma were harvested. T cell receptor beta-chain (TCRβ) profiling was performed though high-throughput sequencing (HTS), and IMonitor, MiXCR and VDJtools were used to analyze the characteristics of the TCR repertoire. Read More