53 results match your criteria: "Department of Clinical Research in Tumor Immunology[Affiliation]"

Current immunotherapy for thymic epithelial tumors: a narrative review.

Mediastinum

October 2024

Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.

Background And Objective: Thymic epithelial tumors (TETs) are the most common neoplasm of the prevascular mediastinal compartment and are characterized by their rarity and variable clinical presentation. The present study aimed to explore the current management of patients with TET with a special focus on immunotherapy for advanced disease.

Methods: Relevant studies published between 1981 and 2024 were searched in PubMed using search terms "Thymoma", "Thymic cancer", "Myasthenia gravis", "Radiation therapy", "Surgery", and "Immunotherapy".

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Animal models of N-butyl-N-(4-hydroxy butyl) nitrosamine (BBN)-induced urothelial carcinoma (UC), particularly bladder cancer (BC), have long been established. However, the rare incidence of BBN-induced upper urinary tract UC (UTUC), which originates from the same urothelium as BC, remains elusive. The scarcity of animal models of UTUC has made it challenging to study the biology of UTUC.

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Adipose tissue and bacterial flora are involved in metabolism in the human body. However, the relationship between the two remains unclear. Recently, the presence of circulating bacterial DNAs has been reported.

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Background/aim: We herein examined T cell immunity in esophageal cancer patients with and without Helicobacter pylori infection to establish a foundation for immunotherapeutic strategies targeting esophageal cancer in the presence of H. pylori infection.

Materials And Methods: Twenty-six patients with esophageal squamous cell carcinoma between 2015 and 2017 were enrolled in the present study.

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Background: CCR8-expressing regulatory T cells (Tregs) are selectively localized within tumors and have gained attention as potent suppressors of anti-tumor immunity. This study focused on CCR8 Tregs and their interaction with CD8 T cells in the tumor microenvironment of human lung cancer. We evaluated their spatial distribution impact on CD8 T cell effector function, specifically granzyme B (GzmB) expression, and clinical outcomes.

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Article Synopsis
  • * Researchers developed a new model called MEnet that uses DNA methylation data from various human tissues to predict cell types and their immune status more effectively than existing methods.
  • * MEnet not only proved to be more accurate and faster but also allowed researchers to discover immune cell profiles that could indicate cancer prognosis, suggesting its potential for use in clinical applications.
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Cutibacterium acnes-derived extracellular vesicles promote tumor growth in renal cell carcinoma.

Cancer Sci

August 2024

Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.

Bacterial flora are present in various parts of the human body, including the intestine, and are thought to be involved in the etiology of various diseases such as multiple sclerosis, intestinal diseases, cancer, and uterine diseases. In recent years, the presence of bacterial 16S rRNA genes has been revealed in blood, which was previously thought to be a sterile environment, and characteristic blood microbiomes have been detected in various diseases. However, the mechanism and the origin of the bacterial information are unknown.

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Tetracyclines enhance antitumor T-cell immunity via the Zap70 signaling pathway.

J Immunother Cancer

April 2024

Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.

Background: Cancer immunotherapy including immune checkpoint inhibitors is only effective for a limited population of patients with cancer. Therefore, the development of novel cancer immunotherapy is anticipated. In preliminary studies, we demonstrated that tetracyclines enhanced T-cell responses.

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Purpose: The NY-ESO-1 antigen is highly immunogenic and often spontaneously induces an immune response in patients with cancer. We conducted a large-scale multicenter cohort study to investigate the utility of serum NY-ESO-1 and p53 antibodies as predictive markers for the postoperative recurrence of gastric cancer. Here, we examined the usefulness of pre-treatment NY-ESO-1 and p53 antibodies as tumor markers for the diagnosis of gastric cancer in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9).

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PD-1 expression on tumor cells: a new target for cancer therapy.

Transl Lung Cancer Res

January 2024

Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.

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Background: No reliable marker has been identified to predict postoperative recurrence of gastric cancer. We designed a clinical trial to investigate the utility of serum NY-ESO-1 antibody responses as a predictive marker for postoperative recurrence in gastric cancer.

Methods: A multicenter prospective study was conducted between 2012 and 2021.

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Forkhead box P3 (Foxp3)-expressing regulatory T (Treg) cells play essential roles in immune homeostasis but also contribute to establish a favorable environment for tumor growth by suppressing anti-tumor immune responses. It is thus necessary to specifically target tumor-infiltrating Treg cells to minimize effects on immune homeostasis in cancer immunotherapy. However, molecular features that distinguish tumor-infiltrating Treg cells from those in secondary lymphoid organs remain unknown.

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Article Synopsis
  • This study is the first to investigate the significance of circulating bacterial DNA in patients with renal cell carcinoma (RCC).
  • Researchers analyzed serum extracellular vesicles from 88 RCC patients and 10 healthy individuals, finding three types of bacterial DNA: Bacteroidia, TM7-1, and Sphingomonadales.
  • A newly created BTS index, based on this bacterial DNA, effectively diagnosed RCC and indicated that higher levels of Bacteroidia DNA were linked to worse patient outcomes during nivolumab treatment.
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Introduction: Regulatory T cells (Tregs) have attracted attention as a novel therapeutic target to augment the clinical efficacy of immunotherapy. We conducted phase Ia and Ib trials to examine the safety and efficacy of the anti-CCR4 antibody, KW-0761 (mogamulizumab), which may eliminate effector Tregs (eTregs). We herein overviewed the results of these trials, presented cases with a durable clinical response, and investigated factors associated with the clinical effects of KW-0761.

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A randomized phase 2 study on demeclocycline in patients with mild-to-moderate COVID-19.

Sci Rep

August 2023

Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

Tetracyclines exhibit anti-viral, anti-inflammatory, and immunomodulatory activities via various mechanisms. The present study investigated the efficacy and safety of demeclocycline in patients hospitalized with mild-to-moderate COVID-19 via an open-label, multicenter, parallel-group, randomized controlled phase 2 trial. Primary and secondary outcomes included changes from baseline (day 1, before the study treatment) in lymphocytes, cytokines, and SARS-CoV-2 RNA on day 8.

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Background: The treatment efficacy of immune checkpoint inhibitors (ICIs) is limited, and biomarkers that identify responders are urgently needed. We investigated whether C-reactive protein (CRP) kinetics are associated with the treatment efficacy of ICIs and prognosis in oesophagogastric cancers.

Methods: We analysed 76 gastric cancer patients treated with nivolumab monotherapy.

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Although regulatory T cells (Treg) are inhibitory immune cells that are essential for maintaining immune homeostasis, Tregs that infiltrate tumor tissue promote tumor growth by suppressing antitumor immunity. Selective reduction of tumor-infiltrating Tregs is, therefore, expected to activate antitumor immunity without affecting immune homeostasis. We previously reported that selective Treg depletion targeted by a C-C motif chemokine receptor 8 (CCR8) resulted in induction of strong antitumor immunity without any obvious autoimmunity in mouse models.

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Regulatory T cells (Tregs) contribute to the formation of a tumor-immunosuppressive microenvironment. CCR8 is reportedly selectively expressed in tumor Tregs, and an anti-CCR8 Ab can exert potent antitumor effects by eliminating intratumor Tregs in murine tumor models. In this study, we analyzed changes to intratumor immunity after anti-CCR8 Ab administration, especially in CD8+ T cells, which are involved in cancer cell killing, using the CT26 colorectal carcinoma mouse model.

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T cell immunity in interstitial lung disease with non-small cell lung cancer patients.

Lung Cancer

August 2023

Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.

Article Synopsis
  • This study explores T cell profiles and functions in lung tissues from non-small cell lung cancer (NSCLC) patients with and without interstitial lung disease (ILD) to understand the risks associated with immunotherapy, specifically immune checkpoint inhibitors (ICIs).
  • Researchers found that NSCLC patients with ILD had higher levels of certain T cell subtypes and immune checkpoint molecules compared to those without ILD, indicating a potentially different immune response.
  • The data suggests that Treg cells could hinder the production of key cytokines, which may contribute to the risk of pneumonitis in patients undergoing immunotherapy, underscoring the need for careful management in these patients.
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Minocycline is often administered prophylactically or therapeutically to non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for skin rash as an adverse event. We examined the effects of minocycline on the outcomes of EGFR-mutant NSCLC treated with first-line EGFR-TKIs based on a single-center retrospective analysis. In this retrospective cohort study, data were collected on NSCLC patients treated with first-line EGFR-TKIs between January 2010 and June 2021.

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The potential clinical utility of cell-free DNA for gastric cancer patients treated with nivolumab monotherapy.

Sci Rep

April 2023

Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.

To assess the potential clinical utility of cell-free DNA (cfDNA)-based biomarkers for identifying gastric cancer (GC) patients who benefit from nivolumab. From 31 GC patients treated with nivolumab monotherapy (240 mg/body, Bi-weekly) in 3rd or later line setting, we prospectively collected blood samples at baseline and before the 3rd dose. We compared cfDNA-based molecular findings, including microsatellite instability (MSI) status, to tissue-based biomarkers.

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Article Synopsis
  • This study examines the role of tertiary lymphoid structures (TLSs) in esophageal cancer (EC) and their potential to improve patient outcomes. //! -
  • Researchers analyzed 316 surgical specimens to assess the density and maturity of TLSs, finding that higher density was linked to earlier cancer stages, fewer invasions, better nutrition indicators, and longer survival. //! -
  • In a follow-up study involving 34 patients receiving anti-PD-1 therapy, higher TLS density correlated with better response to treatment and increased survival rates, highlighting the significance of TLS characteristics in cancer prognosis. !*
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Peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer patients.

Sci Rep

October 2022

Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Anti-programmed cell death-1 (PD-1) therapy exerts beneficial effects in a limited population of cancer patients. Therefore, more accurate diagnostics to predict the efficacy of anti-PD-1 therapy are desired. The present study investigated whether peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer (NSCLC) patients.

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Article Synopsis
  • The study investigates the immune evasion properties of cancer stem-like cells (CSLCs) in liver cancer, which are linked to poor prognosis and high rates of metastasis.
  • Researchers created CSLCs from a liver cancer cell line and analyzed their gene expression related to immune evasion, finding that these cells had altered markers compared to regular cancer cells.
  • Results indicated that CSLCs showed resistance to being targeted by natural killer (NK) cells, contributing to larger tumor growth in experiments with mice, highlighting a potential mechanism for immune evasion in liver cancer.
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The tissue-resident marker CD103 on peripheral blood T cells predicts responses to anti-PD-1 therapy in gastric cancer.

Cancer Immunol Immunother

January 2023

Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Since clinical benefits are limited to a subset of patients, we aimed to identify peripheral blood biomarkers that predict the efficacy of the anti-programmed cell death protein 1 (PD-1) antibody (nivolumab) in patients with gastric cancer.

Methods: We collected peripheral blood samples from gastric cancer patients (n = 29) before and after treatment with nivolumab and investigated the relationship between the frequency of surface or intracellular markers among nivolumab-binding PD-1CD8 T cells and treatment responses using multicolor flow cytometry.

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