Kenichi Kumagai

Prof. Dr. Kenichi Kumagai

The University of Tokyo Hospital
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Research Focus & Metrics

Academic Career Length

13Years (2014-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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28 March 2014 in World Journal of Surgical Oncology
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YTYoko Tanaka
Yoko Tanaka
HYHiroyuki Yamada
Hiroyuki Yamada
TSTomoyuki Saito
Tomoyuki Saito
KNKazutoshi Nakaoka
Kazutoshi Nakaoka
KKKenichi Kumagai
Kenichi Kumagai
YHYoshiki Hamada
Yoshiki Hamada
Myofibroma is a benign tumor composed of myoid spindle cells. The prevalence of myofibroma in the oral cavity is very low, with the mandible being the most common site. This report describes an adult case of myofibroma that arose on the mandible and includes magnetic resonance imaging (MRI) and positron emission tomography (PET) findings. On the MRI T1-weighted images, the tumor appeared with signal iso-intensity and was highly and heterogeneously enhanced with contrast material. On the T2-weighted images, it appeared with increased signal intensity. 18 F-fluorodeoxyglucose (FDG)-PET imaging showed abnormal strong accumulation of FDG in the left mandibular region. The tumor was removed by marginal resection of the left mandible under general anesthesia. Histopathological findings revealed that the tumor stroma contained abundant thin-walled vessels. The postoperative course was uneventful, and we found no evidence of recurrence at the postoperative 34-month follow-up.

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Takahiro MoriTakahiro Mori
Takahiro Mori
KKKenichi Kumagai
Kenichi Kumagai
KNKeisuke Nasu
Keisuke Nasu
TYTakamasa Yoshizawa
Takamasa Yoshizawa
KKKoji Kuwano
Koji Kuwano
RSRyuji Suzuki
Ryuji Suzuki
(1) Background: Comparable prognoses after definitive chemoradiation therapy (CRT) to surgery alone for esophageal squamous cell carcinoma (ESCC) have been previously reported; however, no robust prognostic markers have been established. The clonality of tumor-infiltrating lymphocytes (TILs) and tumor microenvironments (TMEs) in ESCC relapsed after CRT were examined to explore prognostic markers. (2) Methods: Clonality of TIL and TME were examined in ESCC with and without preceding CRT, as well as oral squamous cell carcinoma (OSCC) and healthy volunteers as controls. The clonality of TIL was assessed by T-cell receptor (TCR) α and β repertoire analyses and evaluated by diversity indices. The TME was assessed by quantitative polymerase chain reaction evaluating PD-L1 and CD8B. (3) Results: The clonal expansion of TIL was significantly induced within ESCCs and OSCCs, when compared to healthy volunteers, and was mostly induced within ESCCs after definitive CRT. Diversity indices of TIL were not associated with the prognosis, but the ratio of PD-L1 mRNA to CD8B mRNA in TME was significantly associated with a poor prognosis after salvage surgery (p = 0.007). (4) Conclusions: The clonal expansion of TIL is induced after definitive CRT for ESCC, and the ratio of PD-L1 mRNA to CD8B mRNA within tumor tissues is a prognostic marker candidate for salvage esophagectomy after CRT.

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TYTakamasa Yoshizawa
Takamasa Yoshizawa
KKKenichi Kumagai
Kenichi Kumagai
RMRyota Matsubara
Ryota Matsubara
KNKeisuke Nasu
Keisuke Nasu
KKKazutaka Kitaura
Kazutaka Kitaura
RSRyuji Suzuki
Ryuji Suzuki
The element chromium (Cr) is a component of several types of alloys found in the environment, or utilized in dentistry, that may cause intraoral metal contact allergy. However, the pathological mechanism of intraoral Cr allergy remains unclear because there is no established animal model of Cr allergy in the oral mucosa. In this study, we established a novel murine model of Cr-induced intraoral metal contact allergy and elucidated the immune response in terms of cytokine profiles and T-cell receptor repertoire. Two sensitizations with Cr plus lipopolysaccharide solution into the postauricular skin were followed by a single Cr challenge of the oral mucosa to generate the intraoral metal contact allergy model. Histological examination revealed that CD3+ T-cells had infiltrated the allergic oral mucosa one day after exposure to the allergen. The increase in T-cell markers and cytokines in allergic oral mucosa was also confirmed via quantitative PCR analysis. We detected Cr-specific T-cells bearing TRAV12D-1-TRAJ22 and natural killer (NK) T-cells in the oral mucosa and lymph nodes. Our model demonstrated that Cr-specific T-cells and potent NKT-cell activation may be involved in the immune responses of Cr-induced intraoral metal contact allergy.

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KKKenichi Kumagai
Kenichi Kumagai
YKYuta Kishi
Yuta Kishi
TSTaiki Suzuki
Taiki Suzuki
AHAkihisa Horie
Akihisa Horie
KKKoji Kawaguchi
Koji Kawaguchi
YHYoshiki Hamada
Yoshiki Hamada
Oral lichen planus (OLP) is a chronic, T cell-mediated inflammatory disorder classified by the World Health Organization as an oral potentially malignant disorder (OPMD). Despite decades of research, its precise etiology remains incompletely understood and involves a complex interplay between genetic predisposition, environmental triggers, and autoimmune-like responses. This review provides a comprehensive update on OLP pathogenesis, emphasizing the role of CD8 positive cytotoxic T lymphocyte-driven basal keratinocyte apoptosis and the skewing of the T-cell receptor (TCR) repertoire. We highlight the significance of the epidermal growth factor receptor (EGFR) signaling pathway as a molecular bridge between chronic inflammation and epithelial proliferation. Furthermore, we discuss a stepwise therapeutic approach that prioritizes the management of the oral microenvironment—specifically Candida colonization and periodontal health—before escalating to immunosuppressive agents. Finally, we explore emerging precision medicine frontiers, including IL-17/IL-23 inhibitors and JAK inhibitors, alongside traditional Japanese Kampo medicine (Hange-shashin-to) and systemic adjuncts like Cepharanthine, offering a contemporary perspective on modern OLP management. This integrative framework redefines OLP not merely as a chronic inflammatory disorder, but as an immunologically sustained, microenvironment-driven, potentially malignant condition.

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KNKeisuke Nasu
Keisuke Nasu
KKKenichi Kumagai
Kenichi Kumagai
TYTakamasa Yoshizawa
Takamasa Yoshizawa
KKKazutaka Kitaura
Kazutaka Kitaura
RMRyota Matsubara
Ryota Matsubara
YHYoshiki Hamada
Yoshiki Hamada
Palladium (Pd) is a component of several alloy types that are widely used in our environment, including several dental alloy types that cause adverse reactions such as hypersensitivity in the oral mucosa. However, the pathological mechanism of intraoral Pd allergies remains unclear because its animal model in the oral mucosa has not been established. In this study, we established a novel murine model of Pd–induced allergies in the oral mucosa, and explored the immune response of cytokine profiles and T cell diversity in terms of the T cell receptor. The Pd–induced allergy mouse was generated by two sensitizations with PdCl2, plus a lipopolysaccharide solution into the postauricular skin followed by a single Pd challenge of the buccal mucosa. Significant swelling and pathological features were histologically evident at five days after the challenge, and CD4–positive T cells producing high levels of T helper 2 type cytokines had accumulated in the allergic oral mucosa. Characterization of the T cell receptor repertoire in Palladium allergic mice indicated that Pd–specific T cell populations were limited in V and J genes but were diverse at the clonal level. Our model demonstrated that a Pd–specific T cell population with Th2 type response tendencies may be involved in the Pd–induced intraoral metal contact allergy.

Verified
Journal Article
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KKKenichi Kumagai
Kenichi Kumagai
YHYoshiki Hamada
Yoshiki Hamada
AHAkihisa Horie
Akihisa Horie
YSYUDAI SHIMIZU
YUDAI SHIMIZU
YOYoshihiro Ohashi
Yoshihiro Ohashi
Kazuhiro KakimiKazuhiro Kakimi
Kazuhiro Kakimi
The immune landscape of tumor-draining lymph nodes (TDLNs) plays a critical role in shaping antitumor responses and influencing prognosis in oral squamous cell carcinoma (OSCC). Among patients with lymph node (LN) metastasis, clinical outcomes vary widely, yet reliable biomarkers for prognostic stratification remain limited. This study aimed to identify immune features in tumors and LNs that differentiate between favorable and poor outcomes in OSCC patients with nodal metastasis. We analyzed T cell receptor (TCR) CDR3 repertoires and the expression of immune-related genes in primary tumors and paired sentinel LNs from OSCC patients who underwent tumor resection and lymphadenectomy. Patients were divided into three groups: Group A (no nodal metastasis), Group B1 (metastasis without recurrence), and Group B2 (metastasis with recurrence). TCR diversity was assessed using the Shannon index. The expression of immune-related genes (e.g., CD3E, CD4, CD8B, FOXP3, CTLA4, IL2, IL4) was measured by quantitative PCR and normalized to GAPDH. TCR diversity was lower in tumors than in non-metastatic LNs, reflecting clonal expansion. Metastatic LNs exhibited tumor-like diversity, suggesting infiltration by tumor-reactive clones. Tumor gene expression did not differ across groups, but LNs from metastatic cases showed the reduced expression of several immune genes. Notably, CD3E, CD8B, CTLA4, IL2, and IL4 distinguished B1 from B2. The immune profiling of LNs offers superior prognostic value over tumor analysis in OSCC patients with LN metastasis. LN-based evaluation may aid in postoperative risk stratification and personalized postoperative management and could inform decisions regarding adjuvant therapy and follow-up strategies.