Details of a Researcher - Tamura, Ryota

Papers - Tamura, Ryota

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Difference in Immunosuppressive Cells Between Peritumoral Area and Tumor Core in Glioblastoma

Tamura R., Ohara K., Sasaki H., Morimoto Y., Kosugi K., Yoshida K., Toda M.

World Neurosurgery (World Neurosurgery) 120 e601 - e610 2018.12

ISSN 18788750

Background: Vascular endothelial growth factor (VEGF)-A and VEGF receptor expression in the peritumoral brain zone (PBZ) differs from that in the tumor core (TC) of glioblastoma. To date, no comparative study has investigated the expression of immunosuppressive cells in the PBZ and TC of glioblastoma. Methods: In 10 patients with newly diagnosed glioblastoma, we used immunohistochemistry to analyze the expression of VEGF-A, hypoxia-inducible factor-1α, programmed cell death-1 (PD-1), Foxp3, CD163, CD4, and CD8 to assess the immunosuppressive microenvironment. Results: The number of Foxp3+ and CD163+ cells was significantly greater in the TC than in the PBZ and correlated with greater expression of hypoxia-inducible factor-1α and VEGF-A in the TC than in the PBZ. The number of CD8+ T cells was lower in the TC than in the PBZ, and the TC had more PD-1+CD8+ T cells compared with the PBZ. These results suggest that the hypoxic condition could be associated with PD-1 expression on lymphocytes, the distribution of Foxp3+ regulatory T cells and CD163+ tumor-associated macrophages. Conclusions: The present study reports the first clinicopathologic features of the differences in immunosuppressive cells and the expression of immune checkpoint molecules between the TC and PBZ of glioblastoma.

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Dual role of macrophage in tumor immunity

Tamura R., Tanaka T., Yamamoto Y., Akasaki Y., Sasaki H.

Immunotherapy (Immunotherapy) 10 ( 10 ) 899 - 909 2018.08

ISSN 1750743X

Macrophages are significant in immune responses, assuming a defensive role. In contrast, macrophages often cause undesirable changes. These reactions are processes by which macrophages express different functional programs in response to microenvironmental signals, defined as M1/M2 polarization. Tumor immunity has been acknowledged for contributing to the elucidation of the mechanism and clinical application in cancer therapy. One of the mechanisms for the refractoriness to cancer immunotherapy is the production of inhibitory cytokines by tumor cells or macrophages. Therefore, therapeutic strategy targeting macrophage or macrophage-derived cytokines may be effective and attractive. This review aims to investigate macrophage-associated pathophysiology and biological behavior in cancers, especially related to microenvironment, such as hypoxia, and current topics regarding some therapies involving macrophages.

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Histopathological vascular investigation of the peritumoral brain zone of glioblastomas

Tamura R., Ohara K., Sasaki H., Morimoto Y., Yoshida K., Toda M.

Journal of Neuro-Oncology (Journal of Neuro-Oncology) 136 ( 2 ) 233 - 241 2018.01

ISSN 0167594X

To date, no histopathological vascular investigation focusing on peritumoral brain zone (PBZ) has been reported for glioblastoma. We analyzed 10 newly diagnosed cases of glioblastomas. For these PBZs, histopathological investigation was performed by hematoxylin–eosin (H&E) staining and immunohistochemistry was analyzed for CD31, CD34, Factor VIII, VEGF, VEGFR-1/2, Ki67, p53 and nestin. Although it was difficult to identify PBZ by H&E, Ki67 and p53 staining, there were apparent differences in nestin staining among PBZ, tumor core (TC), and normal zone (NZ). Therefore, in this study, we divided PBZ from TC and NZ by nestin staining. Differences in histological features, microvessel density, expression of VEGF and its receptors were assessed for PBZ, TC and NZ. The microvessel density, as determined by counting CD31, CD34 and VEGF receptors, and VEGF-A expression were lower in PBZ than TC. The expression patterns for CD31, CD34 and VEGF receptors in vessels show dissociation in PBZ. In addition, the vascular characteristics of the PBZ may correlate with findings of radiographic imaging. We provide the first clinicopathological evidence that PBZ exhibits unique angiogenic characteristics. These in situ observations will help to elucidate the mechanisms of tumor recurrence.

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Severe headache in a patient with meningioma showing extensive dural tail correlates with IgG4-positive plasma cells and eosinophils: A case report and review of literature

Kuranari Y., Tamura R., Mikami S., Ohara K., Toda M., Yoshida K.

Surgical Neurology International (Surgical Neurology International) 9 ( 1 ) 2018

Background: Meningiomas originate from meningothelial cells of the arachnoid membrane. Few cases of meningioma with infiltration of inflammatory cells, such as lymphocytes and plasma cells, have been reported, and the mechanisms underlying meningioma-induced inflammatory reactions have not been fully elucidated. Case Description: In this study, we report an extremely rare case of meningioma with infiltration of both IgG4-positive plasma cells and eosinophils showing extensive dural tail and reactive inflammation of the surrounding arachnoid tissue. The main clinical manifestation was a severe headache, which was improved by surgical excision of the tumor. Conclusion: Only 8 cases of meningioma with IgG4-positive plasma cells have been reported, and only one case exhibited eosinophil infiltration. IgG4-related inflammatory response might mediate inflammation in surrounding tissue, resulting in thickening of the dura adjacent to a meningioma and severe headache. The mechanisms underlying inflammation by meningiomas require further investigation.

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Stem cell-based therapies for neurological disorders

Tamura R, Toda M

AIMS Cell and Tissue Engineering 2 24 - 47 2018