A Study on Theory of Body in Maurice Merleau-Ponty’s Phenomenology ― From the viewpoint of ‘Waza’ in Japanese High School Baseball ―

[EN] This study aims to expand the theory of body in Maurice Merleau‐Ponty’s phenomenology from the viewpoint..

The formation of the Warrior’s Status based on a review of the Hojyo-Ryu Heiho Series

[EN] Various Japanese budo have evolved into their modern form since the Meiji period (1868–1912)

NK cells activated by Interleukin-4 in cooperation with Interleukin-15 exhibit distinctive characteristics

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 宮島 篤, 東京大学教授 北村 俊雄, 東京大学教授 菅野 純夫, 東京大学教授 三宅 健介, 東京大学教授 吉田 進昭, 東京大学特任教授 渡邉 すみ子University of Tokyo(東京大学

Tumor-Infiltrating γδ T Cells Suppress T and Dendritic Cell Function via Mechanisms Controlled by a Unique Toll-like Receptor Signaling Pathway

Summaryγδ T cells are important contributors to innate immunity against cancer, but their regulatory role in controlling immune responses remains largely unknown. Here we report that a dominant γδ1 T cell population among lymphocytes infiltrating breast tumors possessed a potent ability to suppress naive and effector T cell responses and to block the maturation and function of dendritic cells. Adoptive cotransfer experiments demonstrated their in vivo suppressive activity. However, their immunosuppressive activity could be reversed by human Toll-like receptor (TLR) 8 ligands both in vitro and in vivo. siRNA-mediated knockdown experiments revealed that MyD88, TRAF6, IKKα IKKβ, and p38α molecules in γδ1 cells were required for these cells to respond to TLR8 ligands, whereas TAK1, JNK, and ERK molecules did not appear to be involved in functional regulation. These results provide new insights into the regulatory mechanisms of tumor-specific γδ T cells and identify a unique TLR8 signaling pathway linking to their functional regulation

Tumor-Specific Human CD4+ Regulatory T Cells and Their Ligands Implications for Immunotherapy

AbstractRegulatory T cells play an important role in the maintenance of immunological self-tolerance by suppressing immune responses against autoimmune diseases and cancer. Little is known, however, about the nature of the physiological target antigens for CD4+ regulatory T (Treg) cells. Here we report the identification of the LAGE1 protein as a ligand for tumor-specific CD4+ Treg cell clones generated from the tumor-infiltrating lymphocytes (TILs) of cancer patients. Phenotypic and functional analyses demonstrated that they were antigen-specific CD4+ Treg cells expressing CD25 and GITR molecules and possessing suppressive activity on the proliferative response of naive CD4+ T cells to anti-CD3 antibody stimulation. Ligand-specific activation and cell-cell contact were required for TIL102 Treg cells to exert suppressive activity on CD4+ effector cells. These findings suggest that the presence of tumor-specific CD4+ Treg cells at tumor sites may have a profound effect on the inhibition of T cell responses against cancer

Mutation analysis of BRAF and KIT in circulating melanoma cells at the single cell level

信州大学博士（医学）・学位論文・平成25年3月31日授与（甲第945号）・境澤 香里BACKGROUND: The availability of molecular-targeted therapies for the treatment of melanoma has emphasised the need to identify mutations in target genes such as BRAF and KIT. Circulating tumour cells (CTC) are present in the peripheral blood of a significant proportion of cancer patients. METHODS: High molecular weight melanoma-associated antigen (HMW-MAA) was used to isolate melanoma cells from peripheral blood as it is selectively expressed at high levels on melanomas. The HMW-MAA-positive cells were isolated using immunomagnetic beads. After removing CD45(+) cells, CTC were identified by staining with MART-1-and gp100-specific antibodies (HMW-MAA(+), CD45(-), MART-1/gp100(+)). Single, isolated CTC were then subjected to BRAF and KIT mutational analysis. RESULTS: CTC (HMW-MAA(+), CD45(-), MART-1/gp100(+)) were isolated from the blood of 11 patients and BRAF and KIT were sequenced in nine and four patients, respectively. The BRAF sequences identified in the CTC were inconsistent with those identified in autologous melanoma tumours in three patients and the KIT sequences were inconsistent in three patients. In addition, polyclonal BRAF mutations were identified in one patient and concomitant mutations in BRAF and KIT were identified in another patient. CONCLUSION: Melanoma cells show clonal heterogeneity. Therefore, CTC genotyping may be crucial for successful molecular-targeted therapy. British Journal of Cancer (2012) 106, 939-946. doi:10.1038/bjc.2012.12 www.bjcancer.com Published online 26 January 2012 (C) 2012 Cancer Research UKArticleBRITISH JOURNAL OF CANCER. 106(5):939-946 (2012)journal articl