Current Affiliation Organization 【 display / non-display 】

Current Affiliation Organization 【 display / non-display 】

University 【 display / non-display 】

University 【 display / non-display 】

Graduate School 【 display / non-display 】

Graduate School 【 display / non-display 】

External Career 【 display / non-display 】

External Career 【 display / non-display 】

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

Published Papers 【 display / non-display 】

Published Papers 【 display / non-display 】

• Integrated genetic analyses identified T-cell neoplasms other than adult T-cell leukemia/lymphoma in HTLV-1 carriers.

  Naito Y, Yasuda T, Sakihama S, Aiba M, Morichika K, Miyazaki K, Imai H, Masaki A, Tsuyuki T, Shimada S, Yoshimitsu M, Aoyama H, Nakada N, Miyagi T, Tamaki T, Chen BJ, Yuan CT, Fukushima T, Chuang SS, Karube K

  Blood advances ( Blood Advances )  10 ( 5 ) 1670 - 1674   2026.03 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

  　View Summary

  Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1) infection. Although most T-cell neoplasms that develop in HTLV-1 carriers are considered ATLL, non-ATLL T-cell lymphomas (TCLs) could also occur, as documented in only a few case reports. Herein, we presented 14 cases of non-ATLL TCLs arising in HTLV-1 carriers. All TCL cases were serologically positive for HTLV-1 antibody; Southern blot analysis for the viral integration of HTLV-1, in situ hybridization for HTLV-1 basic leucine zipper factor (HBZ-ISH), quantitative real-time PCR for HTLV-1 proviral load (HTLV-1-qPCR), the entire HTLV-1 genome sequence, and target capture sequencing rigorously excluded the possibility of ATLL. Various histological subtypes, such as six nodal T follicular helper cell lymphomas, angioimmunoblastic type/not otherwise specified (nTFHL-AI/NOS), two monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL), two peripheral T-cell lymphomas, NOS (PTCL, NOS), and two anaplastic large cell lymphomas (ALCL), ALK-negative, were included. Each case exhibited immunophenotypes and genetic profiles consistent with its respective histological subtype, but atypical for ATLL. Three nTFHL-AI cases exhibited co-mutations of RHOA p.G17V, TET2, and IDH2 p.R172, characteristic of nTFHL-AI but not of ATLL. Among the molecular analytic modalities included in this study, the combination of HBZ-ISH and HTLV-1-qPCR represented the results obtained from the other more expensive modalities, indicating that this combination is effective in daily practice. When T-cell neoplasms arise in HTLV-1 carriers and exhibit atypical clinical, phenotypical, or genetic features for ATLL, it is recommended to perform HBZ-ISH and HTLV-1-qPCR to distinguish non-ATLL TCLs.

  • Access this article

    DOI
  • Search related information
    PubMed

• Genomic Features of Cervical Cancer in Okinawa, Japan: Preliminary Findings From 23 Patients

  Maemoto Hitoshi, Sakihama Shugo, Karube Kennosuke, Kudaka Wataru, Nakamoto Tomoko, Taira Yusuke, Arakaki Yoshihisa, Shimoji Yuko, Nishie Akihiro

  Cancer Genomics & Proteomics ( International Institute of Anticancer Research )  22 ( 6 ) 1069 - 1080   2025.11 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

  　View Summary

  Background/Aim: Regional differences in genomic mutation profiles of uterine cervical cancer have been reported. Japanese people are divided into two genetic background clusters, originating from mainland Japan and Okinawa. Okinawa is an island prefecture surrounded by the sea, located more than 800 km from the southernmost point of mainland Japan. No studies have examined gene mutation profiles of cervical cancer in Okinawa. This study aimed to investigate the mutation profile of cervical cancer in Okinawa. Patients and Methods: Twenty‑three patients with biopsy‑proven squamous cell carcinoma and adenocarcinoma of the intact uterine cervix who were treated with definitive radiotherapy were analyzed. Genomic DNA was extracted from fresh frozen tissue samples collected by tumor biopsy prior to treatment. Variants of 224 cancer‑related genes were identified using next‑generation sequencing. Results: A total of 29 gene mutations were observed in 16 patients, including nine genes mutated in multiple samples: SCN7A (17%), PIK3CA (13%), FGFR4 (13%), USP6 (13%), SETD2 (9%), KIT (9%), TSC1 (9%), SERPING1 (9%), and NOTCH3 (9%). Compared to a report from mainland Japan, significant differences in mutation frequency were observed in PIK3CA, FBXW7, and ARID1A. Significant mutations in ARID1A, FBXW7, PTEN, TP53, and EP300, reported as relatively common in cervical cancer in other regions were not detected in this study. The rate of 2‑year overall survival and progression‑free survival was 95.5% and 73.4%, respectively. Conclusion: Gene mutation profiles of cervical cancer in Okinawa may differ from those in other regions.

  • Search related information
    CiNii Research

• Coactivation of innate immune suppressive cells induces acquired resistance against combined TLR agonism and PD-1 blockade

  Nishinakamura, H; Shinya, S; Irie, T; Sakihama, S; Naito, T; Watanabe, K; Sugiyama, D; Tamiya, M; Yoshida, T; Hase, T; Yoshida, T; Karube, K; Koyama, S; Nishikawa, H

  SCIENCE TRANSLATIONAL MEDICINE ( Science Translational Medicine )  17 ( 785 ) eadk3160   2025.02 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

  　View Summary

  Immune checkpoint blockade therapy has been successfully applied in clinical settings as a standard therapy for many cancer types, but its clinical efficacy is restricted to patients with immunologically hot tumors. Various strategies to modify the tumor microenvironment (TME), such as Toll-like receptor (TLR) agonists that can stimulate innate immunity, have been explored but have not been successful. Here, we show a mechanism of acquired resistance to combination treatment consisting of an agonist for multiple TLRs, OK-432 (Picibanil), and programmed cell death protein 1 (PD-1) blockade. Adding the TLR agonist failed to convert the TME from immunogenically cold to hot and did not augment antitumor immunity, particularly CD8+ T cell responses, in multiple animal models. The failure was attributed to the coactivation of innate suppressive cells, such as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) expressing CXCR2, through high CXCL1 production by macrophages in the TME upon OK-432 treatment. A triple combination treatment with OK-432, PD-1 blockade, and a CXCR2 neutralizing antibody overcame the resistance induced by PMN-MDSCs, resulting in a stronger antitumor effect than that of any dual combinations or single treatments. The accumulation of PMN-MDSCs was similarly observed in the pleural effusions of patients with lung cancer after OK-432 administration. We propose that successful combination cancer immunotherapy intended to stimulate innate antitumor immunity requires modulation of unwanted activation of innate immune suppressive cells, including PMN-MDSCs.

  • Access this article

    DOI
  • Search related information
    PubMed

• Recent progress in pathological understanding of adult T-cell leukemia/ lymphoma in the new classification era

  Karube, K; Sakihama, S; Takatori, M; Morichika, K; Tamaki, T; Wada, N; Fukushima, T

  LEUKEMIA RESEARCH ( Leukemia Research )  148   107634 - 107634   2025.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

  　View Summary

  Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by Human T-cell leukemia virus type 1 (HTLV-1) infection. Although the 5th Edition of the WHO classification (WHO-5) did not make drastic changes regarding the disease concept of ATLL from the revised 4th Edition of the WHO classification (WHO-4R), WHO-5 newly introduced the essential and desirable diagnostic criteria, namely, "neoplastic lymphoid cell proliferation with mature T-cell phenotype; proven HTLV-1 carriership" and "identification of monoclonal integration of HTLV-1", respectively. To satisfy the desirable criteria, a new diagnostic method using a combination of HBZ-ISH and tax-PCR was introduced for the identification of the HTLV-1 in addition to the conventionally used Southern blot hybridization, especially in the case when only FFPE specimens are available. Morphologically, pleomorphic- and anaplastic large cell-type, account for most cases, while minor variants, ATLL with dermatopathic reaction, angioimmunoblastic T-cell lymphoma-like variant, and classic Hodgkin lymphoma-like variant, should also be noted as diagnostic pitfalls. Phenotypically, about 80 % of ATLL cases show a typical phenotype of CD3 + CD4 +CD25 +CCR4 + , while about 10 % show atypical phenotypes such as T follicular helper cell-like one. Many genetic abnormalities, mainly associated with the TCR signaling pathway, are observed, and most are more frequent in the aggressive type than in the indolent type, except for STAT3, indicating the heterogeneous pathogenic process of ATLL. In this review, we present the latest findings on molecular pathogenesis and histopathological findings of ATLL in the era of the new classification of lymphomas, serving as a basis for future research and classification.

  • Access this article

    DOI
  • Search related information
    PubMed

• A Comprehensive Study of the Immunophenotype and its Clinicopathologic Significance in Adult T-Cell Leukemia/Lymphoma.

  Tamaki T, Karube K, Sakihama S, Tsuruta Y, Awazawa R, Hayashi M, Nakada N, Matsumoto H, Yagi N, Ohshiro K, Nakazato I, Kitamura S, Nishi Y, Miyagi T, Yamaguchi S, Nakachi S, Morishima S, Masuzaki H, Takahashi K, Fukushima T, Wada N

  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc   36 ( 8 ) 100169 - 100169   2023.03 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

  　View Summary

  Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell tumor caused by human T-lymphotropic virus type 1 (HTLV-1). The typical ATLL immunophenotypes are described in the 2017 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (positive: CD2, CD3, CD5, CD4, and CD25; negative: CD7, CD8, and cytotoxic markers; and partially positive: CD30, CCR4, and FOXP3). However, limited studies are available on the expression of these markers, and their mutual relationship remains unknown. Furthermore, the expression status of novel markers associated with T-cell lymphomas, including Th1 markers (T-bet and CXCR3), Th2 markers (GATA3 and CCR4), T follicular helper markers (BCL6, PD1, and ICOS), and T-cell receptor (TCR) markers, and their clinicopathologic significance is unclear. In this study, we performed >20 immunohistochemical stains in 117 ATLL cases to determine the comprehensive immunophenotypic profile of ATLL, which were compared on the basis of clinicopathologic factors, including morphologic variants (pleomorphic vs anaplastic), biopsy locations, treatments, Shimoyama classification-based clinical subtype, and overall survival. CD3+/CD4+/CD25+/CCR4+ was considered a typical immunophenotype of ATLL, but approximately 20% of cases did not conform to this pattern. Simultaneously, the following new findings were obtained: (1) most cases were negative for TCR-β and TCR-δ (104 cases, 88.9%), indicating the usefulness of negative conversion of TCR expression to provide differentiation from other T-cell tumors; (2) the positivity of CD30 and CD15 and the negativity of FOXP3 and CD3 were significantly associated with anaplastic morphology; and (3) atypical cases, such as T follicular helper marker-positive (12 cases, 10.3%) and cytotoxic molecule-positive cases (3 cases, 2.6%), were identified. No single markers could predict the overall survival among patients with acute/lymphoma subtypes of ATLL. The results of this study illustrate the diversity of ATLL phenotypes. In T-cell tumors occurring in HTLV-1 carriers, the possibility of ATLL should not be eliminated even when the tumor exhibits an atypical phenotype, and the confirmation of HTLV-1 in the tissue is recommended.

  • Access this article

    DOI
  • Search related information
    PubMed

display all >>