Authorship：Lead author,　Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Cancer Research and Clinical Oncology  

Purpose: In a previous study, protein tyrosine phosphatase non-receptor type (PTPN) 3 was identified as an immune checkpoint molecule in lymphocytes, and its potential as a novel target for cancer immunotherapy was anticipated. However, evaluation of dendritic cell (DC) function as antigen-presenting cells is critical for the development of immunotherapy. In this study, we aimed to analyze the biological effect of PTPN3 on DCs induced from human peripheral blood monocytes obtained from healthy individuals. Methods: We used short-interfering RNA to knock down PTP3 in DCs. For DC maturation, we added cancer cell lysate and tumor necrosis factor-α/interferon-α to immature DCs. In the cytotoxic assay, the target cancer cells were SBC5, unmatched with DCs from healthy human leukocyte antigen (HLA)-A24, or Sq-1, matched with DCs. Enzyme-linked immunosorbent assay was used to determine the amount of cytokines. To examine the intracellular signaling system, intracellular staining was used. Results: PTPN3 knockdown significantly increased the number of DCs, expression of CD80 and chemokine receptor (CCR)7, and production of interleukin-12p40/p70 in mature DCs. In the HLA-A24-restricted DC and human lung squamous cell carcinoma cell cytotoxic assay, inhibition of PTPN3 expression in mature DCs induced cytotoxic T lymphocytes with increased production of INF-γ and granzyme B, and enhanced toxicity against cancer cells and migration to cancer. Furthermore, inhibition of PTPN3 expression activated the mitogen-activated protein kinase pathway in DCs. Conclusion: Based on our findings, inhibition of PTPN3 expression could contribute to the development of novel cancer immunotherapies that activate not only lymphocytes but also DCs.

DOI： 10.1007/s00432-023-05250-8

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Authorship：Lead author,　Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：シュプリンガー・ジャパン(株)  

胸腔鏡下に区域切除術または肺葉切除術を施行した患者893例(男性455例、女性438例)を対象に、術中の回収袋による洗浄細胞診(BLC)が臨床的特徴および転帰に及ぼす影響を検討した。ビデオ補助胸腔鏡下手術は4ポート方式で行い、切除臓器の摘出には回収袋(フレキシブルキャッチャー)を使用した。胸腔に挿入した回収袋を洗浄し、洗浄液検体により細胞診検査を実施した。患者をBLC陽性群49例(男性53%、平均70±10歳)と陰性群844例(男性51%、平均68±10歳)の2群に分類した。腫瘍径は陽性群(34±15mm)の方が陰性群(23±11mm)より有意に大きく、病期も陽性群の方が高かった。胸膜浸潤は陽性群(49.0%)の方が陰性群(12.9%)より多く、リンパ節転移と脈管侵襲も陽性群の方が多かった(いずれもP<0.001)。5年生存率は陽性群(73.6%)の方が陰性群(90.2%)より低かったが、BLC陽性は全生存を予測する独立因子でなかった。局所領域再発率は陽性群の方が有意に高く、Cox比例ハザードモデルでBLC陽性は局所領域再発を予測する独立因子であった(HR:1.87、P=0.044)。

Language：English   Publisher：Respiratory Medicine Case Reports  

Background: Primary pulmonary synovial sarcoma (PPSS) is an extremely rare pulmonary malignancy and often poses diagnostic challenges, especially in differentiating it from benign tumors. Case presentation: A 46-year-old woman presented with a slowly enlarging, well-defined nodule in the right lower lobe of the lung. Positron emission tomography showed low FDG uptake (SUVmax 1.52), raising suspicion for a benign lesion. However, histopathologic examination following wedge resection revealed primary pulmonary synovial sarcoma. Subsequently, a right lower lobectomy was performed. The patient has remained recurrence-free for over one year. Conclusions: Surgical resection with clear margins is essential in the management of PPSS. This case highlights the difficulty in distinguishing PPSS from benign lung lesions based on imaging alone, underscoring the importance of pathological confirmation. Accumulation of more reported cases is needed to develop standardized treatment strategies.

DOI： 10.1016/j.rmcr.2025.102236

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Language：English   Publisher：Journal of Immunotherapy  

In the tumor microenvironment, wherein cytotoxic lymphocytes interact with cancer cells, lymphocyte exhaustion, an immune checkpoint inhibitor target, is promoted. However, the efficacy of these inhibitors is limited, and improving response rates remains challenging. We previously reported that protein tyrosine phosphatase nonreceptor type (PTPN) 3 is a potential immune checkpoint molecule for activated lymphocytes and that PTPN3 inhibition should be a focus area for cancer immunotherapy development. Therefore, in this study, we focused on PTPN3-suppressive therapy in terms of lymphocyte exhaustion under hypoxic conditions, which are a cancer microenvironment, and investigated measures for improving the response to anti-programmed death receptor (PD)-1 antibody drugs. We found that PTPN3 expression was upregulated in activated lymphocytes under hypoxic conditions, similar to the findings for other immune checkpoint molecules, such as PD-1, T cell immunoglobulin mucin-3, and lymphocyte-activation gene-3; furthermore, it functioned as a lymphocyte exhaustion marker. In addition, PTPN3-suppressed activated lymphocytes promoted the mammalian target of rapamycin (mTOR)-Akt signaling pathway activation and enhanced proliferation, migration, and cytotoxic activities under hypoxic conditions. Furthermore, PTPN3 suppression in activated lymphocytes increased PD-1 expression and enhanced the antitumor effects of anti-PD-1 antibody drugs against head and neck cancer in vitro and in vivo. These results suggest that the suppression of PTPN3 expression in activated lymphocytes enhances the therapeutic effect of anti-PD-1 antibody drugs in head and neck cancer, especially under hypoxic conditions that cause lymphocyte exhaustion.

DOI： 10.1097/CJI.0000000000000503

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Language：Japanese  

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Language：Japanese   Publisher：(一社)日本外科学会