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en: Characterization of double-negative T cells in colorectal cancers and their corresponding lymph nodes.

en: TCRαβ+ CD4- CD8- double-negative T (DNT) cells are minor populations in peripheral blood, and their roles have mostly been discussed in inflammation and autoimmunity. However, the functions of DNT cells in tumor microenvironment remain to be elucidated. We investigated their characteristics, possible origins and functions in colorectal cancer tissues as well as their corresponding tumor-draining lymph nodes. We found a significant enrichment of DNT cells in tumor tissues compared with their corresponding lymph nodes, especially in tumors with lower T cell infiltration. T cell receptor (TCR) sequence analysis of CD4+ T, CD8+ T and DNT cells indicated that TCR sequences detected in DNT cells were found in CD8+ T cells, but rarely in CD4+ T cells, suggesting that a part of DNT cells was likely to be originated from CD8+ T cells. Through a single-cell transcriptomic analysis of DNT cells, we found that a DNT cell cluster, which showed similar phenotypes to central memory CD8+ T cells with low expression of effector and exhaustion markers, revealed some specific gene expression patterns, including higher GZMK expression. Moreover, in flow cytometry analysis, we found that DNT cells lost production of cytotoxic mediators. These findings imply that DNT cells might function as negative regulators of anti-tumor immune responses in tumor microenvironment.

en: Oncoimmunology

ja: Oncoimmunology


en: Lymphocytes in tumor-draining lymph nodes co-cultured with autologous tumor cells for adoptive cell therapy.

en: Our results imply that tumor-reactive effector T cells were present even in pathologically non-metastatic lymph nodes and could be expanded in vitro in the presence of autologous tumor cells and possibly be applied for ACT.

ja: Lymphocytes from TDLNs resected during surgical operation were cultured with autologous-tumor cells for 2 weeks and evaluated tumor-reactivity by IFNγ ELISPOT assay. We investigated the commonality of T cell receptor (TCR) clonotypes expanded by the co-culture with tumor cells with those of tumor infiltrating lymphocytes (TILs).

en: Journal of Translational Medicine

ja: Journal of Translational Medicine


en: 両眼性の漿液性網膜剥離をきたした急性リンパ性白血病の1例

ja: 両眼性の漿液性網膜剥離をきたした急性リンパ性白血病の1例

en: Japanese Journal of Clinical Ophthalmology

ja: 臨床眼科


en: Survival of mature T cells depends on signaling through HOIP.

en: T cell development in the thymus is controlled by a multistep process. The NF-B pathway regulates T cell development as well as T cell activation at multiple differentiation stages. The linear ubiquitin chain assembly complex (LUBAC) is composed of Sharpin, HOIL-1L and HOIP, and it is crucial for regulating the NF-B and cell death pathways. However, little is known about the roles of LUBAC in T-cell development and activation. Here, we show that in T-HOIP(linear) mice lacking the ubiquitin ligase activity of LUBAC, thymic CD4(+) or CD8(+) T cell numbers were markedly reduced with severe defects in NKT cell development. HOIP(linear) CD4(+) T cells failed to phosphorylate IB and JNK through T cell receptor-mediated stimulation. Mature CD4(+) and CD8(+) T cells in T-HOIP(linear) mice underwent apoptosis more rapidly than control T cells, and it was accompanied by lower CD127 expression on CD4(+)CD24(low) and CD8(+)CD24(low) T cells in the thymus. The enforced expression of CD127 in T-HOIP(linear) thymocytes rescued the development of mature CD8(+) T cells. Collectively, our results showed that LUBAC ligase activity is key for the survival of mature T cells, and suggest multiple roles of the NF-B and cell death pathways in activating or maintaining T cell-mediated adaptive immune responses.

en: Scientific Reports

ja: Scientific Reports


en: Are the equations for the creatinine-based estimated glomerular filtration rate applicable to the evaluation of renal function in Japanese children and adult patients receiving chemotherapy?

en: Equations for the creatinine-based estimated glomerular filtration rate (eGFR) were recently established for Japanese adults (>18 years old) and children (2-11 years old), respectively, but it is unclear whether eGFR can be as useful as 24-h creatinine clearance (CCr) for assessing renal function in patients receiving chemotherapy. This study examined the degree of concordance between eGFR and CCr and the risk factors leading to the overestimation of renal function by eGFR. A total of 53 data points of 19 children and 56 data points of 16 adults who received chemotherapy were analyzed retrospectively. Body mass index, serum creatinine concentration, 24-h urinary creatinine excretion (UCr), and nephrectomy were considered as risk factors for overestimation by eGFR. In the pediatric part of the study, 7 data points from 3 patients who underwent nephrectomy were included. The eGFR in patients with bilateral kidneys overestimated renal function to a greater degree than in patients with a unilateral kidney. In 45.7 % of pediatric patients with bilateral kidneys and in 19.6 % of adult patients, eGFR overestimated renal function. The risk factor for overestimation was lower UCr in pediatric patients with bilateral kidneys and adult patients. Concordance between eGFR and CCr in pediatric patients with a unilateral kidney should be assessed separately from that in patients with bilateral kidneys. In restricting calculation of eGFR to pediatric patients with bilateral kidneys and adult patients without little muscle mass, eGFR may be useful regardless of whether patients are receiving chemotherapy.

en: Clinical and Experimental Nephrology

ja: Clinical and Experimental Nephrology


en: A case of disseminated neonatal herpes simplex virus infection

ja: 臨床研究・症例報告 全身型新生児単純ヘルペスウイルス感染症の1例

en: Japanese Journal of Pediatrics

ja: 小児科臨床


en: Assessment of renal function in Japanese children with malignancies using serum cystatin C.

en: Several factors besides renal function influence serum cystatin C (CysC) levels. The present study evaluates the value of serum CysC and the equation for CysC based estimated glomerular filtration rate (CysC-eGFR) for Japanese children with malignancies. We collected information at 36 time points from 13 patients aged ≤ 17 years with malignancies. We assessed tumor activity, cell recovery phase after chemotherapy, neutropenia phase, inflammation response and medication with granulocyte-colony stimulating factor, steroid, and levothyroxine as risk factors associated with serum CysC levels. Although no 24-h creatinine clearance (CCr) data collected at 36 time points indicated renal dysfunction, serum CysC levels were above and below the reference values at four and five time points, respectively. The frequency of elevated serum CysC levels was higher in patients without therapy or with stable or progressive disease than among those with a complete or partial response (p = 0.0046). The correlation coefficient between CCr and CysC-eGFR was 0.355 (p = 0.054), but this improved to 0.663 (p = 0.0010) when restricted to patients with a complete or partial response. Levels of serum CysC might become elevated regardless of renal function, and CysC-eGFR might become unpredictable during the active phase of tumors. J. Med. Invest. 65:231-235, August, 2018.

en: The Journal of Medical Investigation : JMI


en: Atypical teratoid rhabdoid tumor in the cavernous sinus of a toddler presenting with oculomotor nerve palsy.

en: Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant, and aggressive tumor of infancy. Although the prognosis of ATRT has been extremely poor, recently, the first prospective study for ATRT demonstrated improvement of prognosis. On the other hands, oculomotor nerve palsy is rare in children and the most frequent etiology is congenital. To our knowledge, only a few ATRT cases presenting with oculomotor nerve palsy have been reported, but ATRT originating from the cavernous sinus (CS) has not yet been reported. An 18-month-old girl with right oculomotor nerve palsy was admitted, and a small mass in the right CS was detected with brain MRI. Although she received steroid pulse therapy and antimicrobial therapy, the mass continued to enlarge. One month after admission, the mass was partially resected and diagnosed as ATRT. Multimodal therapy including anthracycline-based chemotherapy, intrathecal therapy, and cranial irradiation was performed. Twenty-nine months after resection, she was alive without tumor relapse, but the oculomotor nerve palsy persisted. This is the first reported case of ATRT located in the CS presenting with oculomotor nerve palsy. This case was successfully treated with partial removal of the tumor, a new chemotherapy regimen for ATRT and cranial X-ray irradiation.

en: Child's Nervous System

ja: Child's Nervous System