A5053346773- MicroRNA in disease regulation
- Cancer Immunotherapy and Biomarkers
- Mathematical Biology Tumor Growth
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Blood groups and transfusion
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Hepatocellular Carcinoma Treatment and Prognosis
- CAR-T cell therapy research
- Immunodeficiency and Autoimmune Disorders
- Cancer, Hypoxia, and Metabolism
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Liver Disease Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- MRI in cancer diagnosis
- vaccines and immunoinformatics approaches
- Ferroptosis and cancer prognosis
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cancer, Lipids, and Metabolism
- Medical Imaging and Pathology Studies
- Wnt/β-catenin signaling in development and cancer
- Autoimmune Bullous Skin Diseases
- Hepatitis B Virus Studies
- Liver Diseases and Immunity
Keio University
2016-2025
Aoyama Gakuin University
2024
Center for Cancer Research
2020-2023
National Cancer Institute
2020-2023
National Institutes of Health
2020-2023
European Foundation for the Study of Chronic Liver Failure
2021
Keio University Hospital
2018-2020
Shizuoka City Shimizu Hospital
2018
Yamagata University
2017
Fujieda Municipal General Hospital
2012
Immune cells constitute an important element of tumor tissue. Accumulating evidence indicates their clinicopathological significance in predicting prognosis and therapeutic efficacy. Nonetheless, the combinations immune forming microenvironment association with histological findings remain largely unknown. Moreover, it is unclear which or microenvironments are most prognostically significant. Here, we comprehensively analyzed its intratumor heterogeneity 919 regions 158 hepatocellular...
The PI3K-Akt-mTORC1 axis contributes to the activation, survival, and proliferation of CD4(+) T cells upon stimulation through TCR CD28. Here, we demonstrate that suppression this by deletion p85α or PI3K/mTORC1 inhibitors as well cell-specific raptor, an essential component mTORC1, impairs Th17 differentiation in vitro vivo a S6K1/2-dependent fashion. Inhibition PI3K-Akt-mTORC1-S6K1 downregulation Gfi1, negative regulator differentiation. Furthermore, S6K2, nuclear counterpart S6K1, is...
Immune cells and tumor vessels constitute important elements in tissue; however, their detailed relationship human tumors, including HCC, is still largely unknown. Consequently, we expanded our previous study on the immune microenvironment of HCC analyzed among microenvironment, inflammatory/angiostatic factor expression, angiogenic vessel findings, encapsulating clusters (VETC) macrotrabecular-massive (MTM) patterns.We classified into four distinct immunovascular subtypes...
Neoplastic cancer cells and stroma (including infiltrating immune cells) determine the biology prognosis of cancer. Various types adaptive innate are known to infiltrate stroma. However, patterns spatial distribution cell infiltration as well its association with tumor histology remain poorly understood. To address these issues, we comprehensively analyzed present in lung adenocarcinoma. The principal both were immunohistochemically evaluated predominant histologic components 111...
Naive CD4(+) T cells are activated by antigen-presenting (APCs) and differentiate into distinct types of helper (T(h)) in the lymph node or spleen. Oxygen (O(2)) tension is generally low these secondary lymphoid tissues compared with bloodstream atmosphere. However, effect changes O(2) concentration on differentiation T(h) remains unclear. Here, we established a novel model T(h)-cell differentiation, which mimics physiological conditions. We primed naive under 5% O(2), has been observed...
Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation and graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. Although vitro-expanded antigen-specific induced Tregs (iTregs) have been considered be a promising therapeutic agent against such excessive reactions, instability of iTregs transfer is fundamental problem their clinical application. In...
Abstract Purpose To achieve a historical perspective, the chronological changes in primary liver cancer over 20-year period were investigated at single institution, focusing on shifts etiology and impact imaging pathological findings using The Liver Imaging Reporting Data System. Materials methods A retrospective study of surgically resected 680 patients from 2001 to 2020 resulted 434 with 482 nodules being analyzed. Dynamic contrast-enhanced computed tomography System 2018 classification...
Previously, we advocated the importance of classifying hepatocellular carcinoma (HCC) based on physiological functions. This study aims to classify HCC by focusing liver-intrinsic metabolism and glycolytic pathway in cancer cells. Comprehensive RNA/DNA sequencing, immunohistochemistry, radiological evaluations were performed tissues from training cohort (n=136) validated 916 public samples. was classified using hierarchical clustering compared with previous molecular, histopathological,...
Abstract A 61-year-old female patient with advanced intrahepatic cholangiocarcinoma diagnosed based on imaging and tumor biopsy findings was treated combination therapy comprising gemcitabine, cisplatin, durvalumab. After eight cycles of durvalumab two subsequent maintenance immunotherapy, significant shrinkage enabled conversion surgery R0 resection. The immune microenvironment has a critical role in predicting the efficacy combined immunotherapy some types cancer; however, its remains...
Abstract Regulatory T cells (Tregs) are known to inhibit antitumor immunity, yet the specific mechanism by which intratumoral Tregs promote tumor growth remains unclear. To better understand roles of Tregs, we selectively depleted tumor-infiltrating using anti-CD25-F(ab′)2 near-infrared photoimmunotherapy. Depletion induced transient but synchronized IFNγ expression in CD8 and natural killer (NK) cells. Despite small fraction NK contained within examined tumors, produced these led efficient...
Epithelial-mesenchymal transition (EMT) promotes invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the importance its reverse process, mesenchymal-epithelial (MET), for PDAC remains unclear. We aimed to characterize histological finding "focal differentiation" in at perineural sites context MET investigate role Schwann cells inducing tumor MET. Tumor differentiation immunohistochemical expressions E-cadherin, SMAD3, vimentin were examined 168 tissues. Four cell...
Significance Immune tolerance is crucial to prevent harmful immune reactions against self-antigens and well operated by central thymic peripheral tissue tolerance. However, had been investigated under influence from We successfully decoupled utilizing autoantigen-deficient thymus. Experiments revealed that self-antigen presentation in steady state initiated proliferation but subsequent disappearance of autoreactive CD4 + T cells draining lymph nodes. After screening representative...
Interleukin-27 (IL-27) is an immunoregulatory cytokine whose essential function to limit immune responses. We found that the gene encoding cholesterol 25-hydroxylase (Ch25h) was induced in CD4
Aim Emerging evidence suggests a promising role for tumor stromal factors in characterizing patients with various types of malignancies, including hepatocellular carcinoma (HCC). We quantified the amount collagen and elastin fibers HCC samples aim clarifying clinico‐patho‐radiological significance fiber deposition HCC. Methods computed using digital image analysis whole‐slide images Elastica van Gieson‐stained tissues from 156 surgically resected HCCs. Furthermore, we assessed correlations...
<b><i>Introduction:</i></b> Immunotherapy is becoming a promising approach for unresectable-hepatocellular carcinoma (HCC); the anti-tumor response affected by tumor microenvironment (TME). Although Wnt/β-catenin mutations are reported to cause non-inflamed phenotype, their role on TME remains controversial. We aimed clarify heterogeneity of immunophenotype in HCC with mutations. <b><i>Methods:</i></b> This study includes 152 resected HCCs;...