A5033862426- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Colorectal Cancer Treatments and Studies
- Immune cells in cancer
- Colorectal Cancer Surgical Treatments
- HER2/EGFR in Cancer Research
- Lung Cancer Research Studies
- Cancer therapeutics and mechanisms
- Colorectal and Anal Carcinomas
- Cancer Research and Treatments
- Gastric Cancer Management and Outcomes
- T-cell and Retrovirus Studies
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Phagocytosis and Immune Regulation
- Genetic factors in colorectal cancer
- Lung Cancer Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Stress, Anesthesia, and Immune Response
- interferon and immune responses
- Heat shock proteins research
Okayama University
2021-2025
Kindai University
2013-2025
Okayama University Hospital
2025
National Cancer Center Hospital East
2016-2024
Chiba Cancer Center
2019-2024
Okayama Shoka University
2023-2024
Institute of Cancer Research
2023
National Cancer Center
2017-2021
St. Luke's International Hospital
2021
Cancer Hospital of Chinese Academy of Medical Sciences
2021
Significance PD-1 blockade is a cancer immunotherapy effective in various types of cancer. However, we observed rapid progression, called hyperprogressive disease (HPD), ∼10% advanced gastric patients treated with anti–PD-1 monoclonal antibody. Tumors HPD possessed highly proliferating FoxP3 + Treg cells after treatment, contrasting their reduction non-HPD tumors. In vitro augmented proliferation and suppressive activity human cells. Likewise, murine that were deficient signaling more...
This is a phase Ib trial of regorafenib plus nivolumab for gastric and colorectal cancer.Enrolled patients received in dose-finding part to estimate the maximum tolerated dose. Additional were enrolled dose-expansion part. Regorafenib 80-160 mg was administered once daily 21 days on/7 off with 3 mg/kg every 2 weeks. The primary end point dose-limiting toxicity (DLT) during first 4 weeks recommended dose.Fifty (25 each cancer) enrolled. All had ≥ previous lines chemotherapy, including...
The clinical efficacy of anti-PD-1 (programmed cell death-1) monoclonal antibody (mAb) against cancers with oncogenic driver gene mutations, which often harbor a low tumor mutation burden, is variable, suggesting different contributions each to immune responses. Here, we investigated the immunological phenotypes in microenvironment (TME) epidermal growth factor receptor (EGFR)-mutated lung adenocarcinomas, for mAb largely ineffective. Whereas EGFR-mutated adenocarcinomas had noninflamed TME,...
Several studies have established a correlation between the VEGF-VEGFR2 axis and an immunosuppressive microenvironment; this immunosuppression can be overcome by anti-angiogenic reagents, such as ramucirumab (RAM). However, little is known about immunological impact of reagents within tumor microenvironment in human clinical samples. This study aimed at investigating effects RAM on microenvironmental immune status cancers.
Preoperative chemoradiotherapy (CRT) and surgical resection are the standard treatment for locally advanced rectal cancer (LARC). Combining immune checkpoint inhibitors with radiation suggests a promising approach enhancing efficacy. We investigated efficacy of CRT followed by nivolumab surgery in patients LARC.In phase I, we feasibility sequentially combined CRT, 5 cycles nivolumab, radical surgery. In II, microsatellite stable (MSS) instability-high (MSI-H) LARC were evaluated.Three I...
BACKGROUNDPrecise stratification of patients with non-small cell lung cancer (NSCLC) is needed for appropriate application PD-1/PD-L1 blockade therapy.METHODSWe measured soluble forms the immune-checkpoint molecules PD-L1, PD-1, and CTLA-4 in plasma advanced NSCLC before blockade. A prospective biomarker-finding trial (cohort A) included 50 previously treated who received nivolumab. retrospective observational study was performed any therapy (cohorts B C), cytotoxic chemotherapy D), or...
Patients treated with immune checkpoint blockade (ICB) sometimes experience immune-related adverse events (irAEs), requiring immuno-suppressive drugs such as corticosteroids despite the possibility that immunosuppression may impair antitumor effects of ICB. Here, we address dilemma using for treatment irAEs induced by ICB augments neoantigen-specific CD8+ T cell responses, resulting in tumor regression. In our model, simultaneous, but not late, administration impaired responses reduction...
Classic Hodgkin lymphoma (cHL) responds markedly to PD-1 blockade therapy, and the clinical responses are reportedly dependent on expression of major histocompatibility complex class II (MHC-II). This dependence is different from other solid tumors, in which MHC I (MHC-I)/CD8+ T-cell axis plays a critical role. In this study, we investigated role MHC-II/CD4+ antitumor effect cHL. cHL, MHC-I was frequently lost, but MHC-II maintained. CD4+ T cells highly infiltrated tumor microenvironment...
Although profiling of gene expression and alterations by next-generation sequencing (NGS) to predict the primary tumor site guide molecularly targeted therapy might be expected improve clinical outcomes for cancer unknown (CUP), our knowledge, no trial has previously evaluated this approach.To assess use site-specific treatment, including based on NGS results, patients with CUP.This phase 2 was conducted at 19 institutions in Japan enrolled 111 untreated unfavorable subset CUP between March...
PD-1 blockade exerts antitumor effects by reinvigorating tumor antigen–specific CD8+ T cells. Whereas neoantigens arising from gene alterations in cancer cells comprise critical antigens immunity, a subset of non–small cell lung cancers (NSCLCs) harboring substantial mutation burden (TMB) lack the microenvironment (TME), which results resistance to therapy. To overcome this resistance, clarifying mechanism(s) impairing immunity highly mutated NSCLCs is an urgent issue. Here, we showed that...
To evaluate the detailed immunosuppressive role(s) of PD-L2 given that its remains unclear in PD-1 signal blockade therapy animal models and humans.We generated mouse cell lines harboring various status PD-L1/PD-L2 evaluated tumor growth phenotypes tumor-infiltrated lymphocytes using several blockades models. In humans, correlation between immune-related gene expression CD274 (encoding PD-L1) or PDCD1LG2 PD-L2) was investigated The Cancer Genome Atlas (TCGA) datasets. addition, PD-L1 cells...
Abstract Combination therapy with anti‐cytotoxic T lymphocyte‐associated protein 4 (CTLA‐4) and anti‐programmed death‐1 (PD‐1) monoclonal antibodies (mAbs) has dramatically improved the prognosis of patients multiple types cancer, including renal cell carcinoma (RCC). However, more than half RCC fail to respond this therapy. Regulatory cells (Treg cells) are a subset highly immunosuppressive CD4 + that promote immune escape tumors by suppressing effector in tumor microenvironment (TME)...