Comparative assessment of autologous and allogeneic iNKT cell transfer in iNKT cell-based immunotherapy.

Invariant natural killer T (iNKT) cells are a small subset of T lymphocytes that release large amounts of cytokines such as IFN-γ and exhibit cytotoxic activity upon activation, inducing strong anti-tumor effects. Harnessing the anti-tumor properties of iNKT cells, iNKT cell-based immunotherapy has been developed to treat cancer patients. In one of the iNKT cell-based immunotherapies, two approaches are utilized, namely, active immunotherapy or adoptive immunotherapy, the latter involving the expansion and subsequent administration of iNKT cells.

Anatomical and clinical factors associated with infrapopliteal arterial bypass outcomes in patients with chronic limb-threatening ischemia.

The aim of this study was to identify anatomical and clinical factors associated with limb-based patency (LBP) loss, major adverse limb events (MALEs), and poor amputation-free survival (AFS) after an infrapopliteal arterial bypass (IAB) surgery according to the Global Limb Anatomic Staging System. A retrospective analysis of patients undergoing IAB surgery between January 2010 and December 2021 at a single institution was performed. Two-year AFS, freedom from LBP loss, and freedom from MALEs were assessed using the Kaplan-Meier method.

Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients.

Purpose: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs.

Methods: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs.

Rapid and Convenient Single-Chain Variable Fragment-Employed Electrochemical C-Reactive Protein Detection System.

Although IgG-free immunosensors are in high demand owing to ethical concerns, the development of convenient immunosensors that alternatively integrate recombinantly produced antibody fragments, such as single-chain variable fragments (scFvs), remains challenging. The low affinity of antibody fragments, unlike IgG, caused by monovalent binding to targets often leads to decreased sensitivity. We improved the affinity owing to the bivalent effect by fabricating a bivalent antibody-enzyme complex (AEC) composed of two scFvs and a single glucose dehydrogenase, and developed a rapid and convenient scFv-employed electrochemical detection system for the C-reactive protein (CRP), which is a homopentameric protein biomarker of systemic inflammation.

Progress in Natural Killer T Cell-Based Immunotherapy for Cancer: Use of Allogeneic and Gene-Edited Cells.

Immune cell therapy has received attention in the clinical setting. However, current chimeric antigen receptor T cell therapies require individualized manufacturing based on patient cells, resulting in high costs and long processing times. Allogeneic immune cell therapy, which involves the use of immune cells from other donors, is emerging as a promising alternative that offers multiple advantages, including off-the-shelf availability, standardized manufacturing, and potentially stronger effector functions.

Anti-Vα24Jα18 TCR Antibody Tunes iNKT Cell Responses to Target and Kill CD1d-negative Tumors in an FcγRII (CD32)-dependent Manner.

Unlabelled: Invariant natural killer T (iNKT) cells play an essential role in antitumor immunity by exerting cytotoxicity and producing massive amounts of cytokines. iNKT cells express invariant T-cell receptors (TCR) to recognize their cognate glycolipid antigens such as α-galactosylceramide (α-GalCer) presented on CD1d. We recently reported that iNKT cells recognize CD1d-negative leukemia cell line K562 in a TCR-dependent manner.

Targeting PD-1/PD-L1 inhibits rejection in a heterotopic tracheal allograft model of lung transplantation.

Immune checkpoint molecules such as programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have revolutionized the field of lung cancer treatment. As part of our study, we examined the role of these proteins in acute rejection in a mouse model of heterotopic tracheal transplantation. Recipient mice were untreated (Allo group) or treated with anti-PD-L1 (aPDL1 group) or PD-L1 Fc recombinant protein (PD-L1 Fc group).

Anti-CD20 Antibody and Calcineurin Inhibitor Combination Therapy Effectively Suppresses Antibody-Mediated Rejection in Murine Orthotopic Lung Transplantation.

Antibody-mediated rejection (AMR) is a risk factor for chronic lung allograft dysfunction, which impedes long-term survival after lung transplantation. There are no reports evaluating the efficacy of the single use of anti-CD20 antibodies (aCD20s) in addition to calcineurin inhibitors in preventing AMR. Thus, this study aimed to evaluate the efficacy of aCD20 treatment in a murine orthotopic lung transplantation model.

[Cancer Immunotherapy Using Allogeneic NKT Cells].

We have developed autologous NKT cell-targeted immunotherapy for lung cancer and head and neck cancer at Chiba University. We induce α-galactosylceramide(αGalCer)-pulsed antigen-presenting cells(APCs)from patients' peripheral blood mononuclear cells(PBMCs)in vitro and give them back to the patients. We transferred them intravenously to patients with lung cancer and demonstrated the potential to improve survival time.

CD69 Imposes Tumor-Specific CD8+ T-cell Fate in Tumor-Draining Lymph Nodes.

Tumor-specific CD8+ T cells play a pivotal role in antitumor immunity and are a key target of immunotherapeutic approaches. Intratumoral CD8+ T cells are heterogeneous; Tcf1+ stemlike CD8+ T cells give rise to their cytotoxic progeny-Tim-3+ terminally differentiated CD8+ T cells. However, where and how this differentiation process occurs has not been elucidated.

Regeneration of invariant natural killer T (iNKT) cells: application of iPSC technology for iNKT cell-targeted tumor immunotherapy.

Invariant natural killer T (iNKT) cells are a subset of innate-like T cells restricted by a major histocompatibility complex (MHC) class I-like molecule, CD1d. iNKT cells express an invariant T cell receptor (TCR) encoded by Vα14 Jα18 in mice and Vα24 Jα18 in humans and are activated by recognizing glycolipid antigens, such as α-galactosylceramide (αGalCer), presented by CD1d. iNKT cells exhibit anti-tumor activity via their NK-like cytotoxicity and adjuvant activity.

Successful Identification of a Novel Therapeutic Compound for Hepatocellular Carcinoma Through Screening of ADAM9 Inhibitors.

Background/aim: MHC-class I-related chain A (MICA) functions as a ligand for natural killer group D, an activating receptor on natural killer (NK) cells, and its expression correlates with the carcinogenesis and progression of hepatocellular carcinoma (HCC). Although membranous MICA (mMICA) activates NK cells, soluble forms of MICA (sMICA), shed by cleaving enzymes, such as A disintegrin and metalloprotease (ADAM) 9, suppress NK cells. Therefore, the prevention of MICA shedding through the inhibition of ADAM9 has the potential to activate cancer immunity.

Interferon-gamma Release Assay-positive Granulomatous Interstitial Nephritis in a Patient with a History of Diffuse Large B Cell Lymphoma.

Tuberculosis is a common etiology of granulomatous interstitial nephritis (GIN). However, the absence of evidence of lung involvement and lack of mycobacterial isolation in cultures make the etiological diagnosis and treatment decision challenging. We herein report a 46-year-old man with severe renal failure, a persistent fever, and a history of lymphoma.

Immunomodulatory Cell Therapy Using αGalCer-Pulsed Dendritic Cells Ameliorates Heart Failure in a Murine Dilated Cardiomyopathy Model.

Background: Dilated cardiomyopathy (DCM) is a life-threatening disease, resulting in refractory heart failure. An immune disorder underlies the pathophysiology associated with heart failure progression. Invariant natural killer T (iNKT) cell activation is a prospective therapeutic strategy for ischemic heart disease.

Extended-synaptotagmin 1 engages in unconventional protein secretion mediated via SEC22B vesicle pathway in liver cancer.

Protein secretion in cancer cells defines tumor survival and progression by orchestrating the microenvironment. Studies suggest the occurrence of active secretion of cytosolic proteins in liver cancer and their involvement in tumorigenesis. Here, we investigated the identification of extended-synaptotagmin 1 (E-Syt1), an endoplasmic reticulum (ER)-bound protein, as a key mediator for cytosolic protein secretion at the ER-plasma membrane (PM) contact sites.

Antibodies against complement component C5 prevent antibody-mediated rejection after lung transplantation in murine orthotopic models with skin-graft-induced pre-sensitization.

Objective: Antibody-mediated rejection (AMR) could induce acute or chronic graft failure during organ transplantation. Several reports have shown that anti-C5 antibodies are effective against AMR after kidney transplantation. However, few reports have assessed the efficacy of anti-C5 antibodies against AMR after lung transplantation.

Effect of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma Harboring Mutation in Early Clinical Experience.

Atezolizumab plus bevacizumab (ATZ/BV) treatment is a combined immunotherapy consisting of immune checkpoint inhibitor (ICI) and anti-vascular endothelial growth factor monoclonal antibody, which has brought a major paradigm shift in the treatment of unresectable hepatocellular carcinoma (HCC). Gain-of-function mutation of contributes to resistance of ICI monotherapy through the framework of non-T-cell-inflamed tumor microenvironment. However, whether mutation renders resistance to ATZ/BV similar to ICI monotherapy remains to be elucidated.

Continuity of diabetes care among elderly Japanese patients: a medical record review study in a specialized diabetes clinic.

Aims: Continuity of diabetes care is relevant among elderly patients. The aim of this study is to investigate the impact of clinical characteristics on continuing outpatient visits to a specialized diabetes clinic in elderly Japanese patients with diabetes.

Methods: We included outpatients with type 2 diabetes aged ≥ 65 years who first visited our clinic from 2006 to 2009.

Extracellular PKCδ signals to epidermal growth factor receptor for tumor proliferation in liver cancer cells.

Protein kinase C delta (PKCδ) is a multifunctional PKC family member and has been implicated in many types of cancers, including liver cancer. Recently, we have reported that PKCδ is secreted from liver cancer cells, and involved in cell proliferation and tumor growth. However, it remains unclear whether the extracellular PKCδ directly regulates cell surface growth factor receptors.

[A 73-year-old man with polyradiculopathy and multiple cranial neuropathies emerging separate from the originating dermatome of a varicella zoster skin lesion].

A 73-year-old man developed delayed-onset multiple cranial neuropathies of cranial nerves V, VII and VIII, and segmental paresis in the ipsilateral upper extremity related to the C4 to Th1 segment, after all skin lesions with varicella zoster (VZV) on the left neck of the C3-4 dermatome had dried and crusted over. On admission, cerebrospinal fluid (CSF) revealed pleocytosis (all mononuclear cells, 12/μl). Treatment was started with intravenous acyclovir (10 mg/kg, every 8 h for 14 days) and methylprednisolone (1,000 mg/day for 3 days).

[The Basic Research of Antigen-antibody Reaction in Lung Transplantation].

Lung transplantation has become popular in Japan, showing better survival rate than other countries. However, the results are still not satisfactory compared with other solid organ transplantation. One of the reasons for this might be that knowledge on donor-specific antibodies or antibody-related rejection, which has been attracting attention these days, is less than that of kidney or liver transplantation.

Patient characteristics associated with improvement in glycemic control following addition of an oral antidiabetic drug to DPP-4 inhibitor monotherapy in Japanese patients with type 2 diabetes mellitus (JDDM 60).

Aims: The current study evaluated patient demographics and clinical characteristics that associated with HbA1c reduction following addition of one oral antidiabetic drug (OAD) to DPP4i monotherapy.

Methods: A retrospective study was conducted using CoDiC database. Adult T2DM patients treated with sitagliptin monotherapy for ≥ 6 months and adding one OAD were extracted.

Efficacy of Fusion Imaging in Endovascular Revascularization of the Superficial Femoral Artery.

Background: The demand for endovascular revascularization (ER) to treat peripheral artery disease (PAD) has steadily increased. However, ER comes at the cost of increased contrast and radiation exposure, particularly in more complex cases. Fusion imaging is a new technology that may address these issues.