記述言語：英語   出版者・発行元：Nagoya journal of medical science  

Myelodysplastic syndrome is associated with the development of autoinflammatory conditions, such as recurrent fever, polymyalgia, arthralgia, and erythema. Trisomy 8 is a common chromosomal abnormality in patients with myelodysplastic syndrome. Myelodysplastic syndrome with trisomy 8 involves autoinflammatory conditions, especially Behçet's disease-like symptoms with intestinal mucosal damage. MEFV variants, particularly those in exon 10, are pathogenic in familial Mediterranean fever, the most common autoinflammatory disease, presenting typical symptoms such as periodic fever and pleuritis/pericarditis/peritonitis. MEFV variants outside exon 10 are common in Japanese patients with familial Mediterranean fever and are associated with atypical symptoms, including myalgia and erythema. MEFV variants in myelodysplastic syndrome with trisomy 8 have rarely been investigated, although myelodysplastic syndrome with trisomy 8 might develop autoinflammatory conditions similar to those in familial Mediterranean fever. We encountered a 67-year-old man who had myelodysplastic syndrome with trisomy 8 and multiple MEFV variants outside exon 10. He presented with periodic fever, as well as chest/abdominal pain, myalgia, and erythema, although the symptoms did not fulfill the diagnostic criteria of familial Mediterranean fever. We discussed the possibility that these symptoms are modified by MEFV variants outside exon 10 in myelodysplastic syndrome with trisomy 8.

DOI： 10.18999/nagjms.85.1.195

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Hematology  

Genomic deletion of donor–patient-mismatched HLA alleles in leukemic cells is a major cause of relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Mismatched HLA is frequently lost as an individual allele or a whole region in HLA-class I, however, it is downregulated in HLA-class II. We hypothesized that there might be a difference in T cell recognition capacity against epitopes associated with HLA-class I and HLA-class II and consequently such allogeneic immune pressure induced HLA alterations in leukemic cells. To investigate this, we conducted in vitro experiments with T cell receptor-transduced T (TCR-T) cells. The cytotoxic activity of NY-ESO-1-specific TCR-T cells exhibited similarly against K562 cells with low HLA-A*02:01 expression. However, we demonstrated that the cytokine production against low HLA-DPB1*05:01 expression line decreased gradually from the HLA expression level approximately 2-log lower than normal expressors. Using sort-purified leukemia cells before and after HSCT, we applied the next-generation sequencing, and revealed that there were several marked downregulations of HLA-class II alleles which demonstrated consistently low expression from pre-transplantation. The marked downregulation of HLA-class II may lead to decreased antigen recognition ability of antigen-specific T cells and may be one of immune evasion mechanism associated with HLA-class II downregulation.

DOI： 10.1007/s12185-021-03273-w

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PubMed

記述言語：日本語  

DOI： 10.1182/blood-2021-150469

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Therapy  

Adoptively transferred CD19 chimeric antigen receptor (CAR) T cells have led to impressive clinical outcomes in B cell malignancies. Beyond induction of remission, the persistence of CAR-T cells is required to prevent relapse and provide long-term disease control. To improve CAR-T cell function and persistence, we developed a composite co-stimulatory domain of a B cell signaling moiety, CD79A/CD40, to induce a nuclear translocating signal, NF-κB, to synergize with other T cell signals and improve CAR-T cell function. CD79A/CD40 incorporating CD19CAR-T cells (CD19.79a.40z) exhibited higher NF-κB and p38 activity upon CD19 antigen exposure compared with the CD28 or 4-1BB incorporating CD19CAR-T cells (CD19.28z and CD19.BBz). Notably, we found that CD19.79a.40z CAR-T cells continued to suppress CD19+ target cells throughout the co-culture assay, whereas a tendency for tumor growth was observed with CD19.28z CAR-T cells. Moreover, CD19.79a.40z CAR-T cells exhibited robust T cell proliferation after culturing with CD19+ target cells, regardless of exogenous interleukin-2. In terms of in vivo efficiency, CD19.79a.40z demonstrated superior anti-tumor activity and in vivo CAR-T cell proliferation compared with CD19.28z and CD19.BBz CD19CAR-T cells in Raji-inoculated mice. Our data demonstrate that the CD79A/CD40 co-stimulatory domain endows CAR-T cells with enhanced proliferative capacity and improved anti-tumor efficacy in a murine model.

DOI： 10.1016/j.ymthe.2021.04.038

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Scopus

PubMed

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/infdis/jiz491

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

記述言語：日本語   出版者・発行元：(一社)日本血液学会-東京事務局  

記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

J-GLOBAL

記述言語：日本語   出版者・発行元：(一社)日本輸血・細胞治療学会  

J-GLOBAL

記述言語：英語  

J-GLOBAL

開催年月日： 2022年6月

開催年月日： 2021年7月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催年月日： 2021年4月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2019年3月

記述言語：英語  

開催年月日： 2017年12月

記述言語：英語  

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