Article
Immunology
Disha Rao, Johanna A. A. Stunnenberg, Ruben Lacroix, Petros Dimitriadis, Joanna Kaplon, Fabienne Verburg, Paula T. T. van van Royen, Esmee P. Hoefsmit, Kathrin Renner, Christian U. U. Blank, Daniel S. S. Peeper
Summary: Glucose limitation and increased lactic acid levels due to elevated glycolytic activity of tumor cells create a metabolic barrier for tumor infiltrating immune cells. Regulatory T cells (Tregs) are not inhibited in lactic acid-rich environments, and lactic acid enhances the induction of Tregs. Acidicity in the tumor microenvironment can be targeted therapeutically to reduce Treg-mediated immune suppression within tumors.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Engineering, Biomedical
Lingting Shi, Jee Yoon Lim, Lance C. Kam
Summary: Regulatory T cells (Tregs) have the potential to suppress immune response and treat autoimmune diseases. This report investigates the induction of Tregs by modulating the mechanical stiffness of the activating substrate. It was found that Treg induction increased with greater material stiffness and involved oxidative phosphorylation (OXPHOS). Inhibition of ATP synthase reduced Treg induction, while activation of AMPK increased it on softer substrates. This mechanosensitive and OXPHOS-dependent mechanism provides new strategies for enhancing Treg production in cellular immunotherapy.
Article
Oncology
Huanhe Ni, Huanling Zhang, Lin Li, He Huang, Hui Guo, Lin Zhang, Chunwei Li, Jing-Xiao Xu, Cai-Ping Nie, Kui Li, Xiaoshi Zhang, Xiaojun Xia, Jiang Li
Summary: In this study, it was found that increased STING and CCL22 levels, as well as higher levels of FOXP3(+) cells and lower levels of CD8(+) cells in tumor tissues of cervical cancer, predicted poor survival. Activation of STING signaling in cooperation with T cell receptor and other signals promoted iTreg differentiation in both human and murine CD4(+) naive T cells. Additionally, tumor-derived exosomes were found to activate STING signaling in tumor-infiltrated T cells, leading to iTreg expansion.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biology
Severine Menoret, Laurent Tesson, Severine Remy, Victor Gourain, Celine Serazin, Claire Usal, Aude Guiffes, Vanessa Chenouard, Laure-Helene Ouisse, Malika Gantier, Jean-Marie Heslan, Cynthia Fourgeux, Jeremie Poschmann, Carole Guillonneau, Ignacio Anegon
Summary: In this study, a Foxp3-EGFP rat transgenic line was created to genetically tag CD4(+) and CD8(+) FOXP3(+) regulatory T cells. CD4(+)EGFP(+) Treg were found to be 5-10 times more frequent than CD8(+)EGFP(+) Treg. RNAseq analysis provided insights into the transcriptome of CD8(+) Treg, allowing for a better understanding of their phenotype and function.
Article
Biochemistry & Molecular Biology
Baowen Zhuo, Qifan Zhang, Tingyan Xie, Yidan Wang, Zhengliang Chen, Daming Zuo, Bo Guo
Summary: Regulatory T (Treg) cells in human tumors exhibit more potent immunosuppressive activity than peripheral blood Treg cells (PBTRs), which impairs the induction of effective antitumor immunity. This study explores the epigenetic profiles of tumor-infiltrating Treg cells (TITRs) and identifies functional regulatory elements. The researchers found global differences in chromatin accessibility and enhancer landscapes between TITRs and PBTRs, as well as two types of active enhancer formation in TITRs. They also discovered that the AP-1 family motifs are enriched at the enhancer regions of TITRs and validated the role of c-Jun in regulating signature genes of TITRs and Treg cell activation. The findings provide insights into the mechanism of AP-1-mediated activation of TITRs and may contribute to the development of new therapeutic strategies for liver cancer treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Immunology
Deepika Watts, Marthe Janssen, Mangesh Jaykar, Francesco Palmucci, Marc Weigelt, Cathleen Petzold, Angela Hommel, Tim Sparwasser, Ezio Bonifacio, Karsten Kretschmer
Summary: In NOD mice, transient loss of Foxp3(+) Treg cells is sufficient to induce severe insulitis and persistent hyperglycemia. This highlights the vital role of Foxp3(+) Treg cell activity in controlling autoimmune diabetes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ningning Xue, Ying Wang, Hao Cheng, Hantian Liang, Xinzou Fan, Fengqiong Zuo, Xin Zeng, Ning Ji, Qianming Chen
Summary: This study demonstrates the important role of Treg cells in maintaining immune homeostasis in the oral mucosa and proposes a novel disease model of oral inflammation. Furthermore, the results show that Treg cell therapy is effective in suppressing oral inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Christopher Tay, Atsushi Tanaka, Shimon Sakaguchi
Summary: Regulatory T cells (Tregs) in tumor tissues can be selectively targeted to enhance anti-tumor immune responses, while maintaining immune homeostasis in healthy organs. Current strategies such as immune checkpoint blockade (ICB) antibodies and differential targeting of surface and intracellular molecules show promise in this regard. Combining Treg targeting with ICB antibodies may enhance the efficacy of cancer immunotherapy.
Article
Oncology
Shuhei Kobayashi, Tunyanat Wannakul, Kaname Sekino, Yu Takahashi, Yoshiteru Kagawa, Hirofumi Miyazaki, Banlanjo Abdulaziz Umaru, Shuhan Yang, Yui Yamamoto, Yuji Owada
Summary: This study shows that FABP5 in pDCs regulates tumor immunity by controlling lipid metabolism, affecting inflammatory gene expression and supporting T cell generation.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Review
Biochemistry & Molecular Biology
Biaolong Deng, Weiqi Zhang, Yicheng Zhu, Yangyang Li, Dan Li, Bin Li
Summary: Regulatory T (Treg) cells play a critical role in maintaining immune homeostasis and their dysfunction in aged patients may contribute to age-related diseases. Immune therapies targeting Treg cells show promising results in treating cancers and autoimmune diseases. Understanding Treg cell function better may help in developing new immune therapies against aging.
Article
Immunology
Dandan Yang, Xueqiang Zhao, Xin Lin
Summary: Bcl10 plays a critical role in the development and function of regulatory T (Treg) cells, deficiency of which leads to impaired development and suppressive function of Treg cells, even causing lethal autoimmunity. Bcl10-deficient Treg cells can undergo conversion into proinflammatory cells and decrease in effector Treg cell populations. The study provides genetic evidence that Bcl10 is essential for Treg cell development and function.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Athmane Teghanemt, Kara Misel-Wuchter, Jace Heath, Andrew Thurman, Priyanjali Pulipati, Garima Dixit, Ramasatya Geesala, David K. Meyerholz, Thorsten Maretzky, Alejandro Pezzulo, Priya D. Issuree
Summary: Regulatory T (T reg) cells are vital in maintaining tolerance and preventing fatal autoimmunity. This study reveals the importance of Tet enzymes and DNA demethylation in promoting Treg cell differentiation in the thymus. Tet3 is specifically involved in the development of CD4 single-positive thymocytes and plays a critical role in TCR-dependent IL-2 production, which is essential for chromatin remodeling and the upregulation of FoxP3.
Review
Immunology
Farooq Riaz, Zhihui Huang, Fan Pan
Summary: This review discusses the immune-suppressive mechanisms of Treg cells, the post-translational regulations of Foxp3, and the potential therapeutic targets and strategies to target Tregs in the tumor microenvironment. Pharmacological targeting of enzymes involved in PTMs can significantly influence the PTMs of Foxp3, potentially impacting the progression of cancers and autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Zeev Elkoshi
Summary: Tumor-infiltrating lymphocytes, particularly the frequencies of regulatory T cells (Tregs) and CD8+ T cells, are important prognostic markers in cancer. The correlation between intra-tumoral Tregs and survival can vary depending on the type of cancer. This study suggests using the frequency ratio of lymphocytes as the preferred marker in most cancer types, as it shows a direct correlation with survival and is less variable compared to individual lymphocyte frequencies. However, if the frequency of one lymphocyte is highly variable, it may be beneficial to focus on the lymphocyte with a less variable frequency to improve the correlation with survival, especially when the intra-tumoral frequencies of the two species are inversely correlated. The marker selected using this approach may also be a good predictor of checkpoint inhibitor therapy success.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Adrian Liston, Meryem Aloulou
Summary: CD8(+)Foxp3(+) cells, often neglected, have regulatory functions similar to CD4(+)Foxp3(+)Treg cells but with distinct characteristics.
IMMUNOLOGY LETTERS
(2022)
Review
Oncology
Akira Hamada, Junichi Soh, Tetsuya Mitsudomi
Summary: Salvage surgery can be considered as an effective treatment option for patients with locally advanced lung cancer, especially for those with late local recurrence or significant metabolic response. In certain conditions, the accumulation of real-world evidence may be necessary for further evaluation, as phase III trials are often difficult to conduct.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Oncology
Kenichi Suda, Shuta Ohara, Toshio Fujino, Akira Hamada, Masato Chiba, Masaki Shimoji, Toshiki Takemoto, Junichi Soh, Tetsuya Mitsudomi
Summary: PET-negative, solid-type lung cancers are rare subgroup of lung cancers with better prognosis and frequent EGFR mutation.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Toshio Fujino, Kenichi Suda, Kazuko Sakai, Isao Murakami, Shigeki Shimizu, Shuta Ohara, Takamasa Koga, Akira Hamada, Junichi Soh, Kazuto Nishio, Tetsuya Mitsudomi
Summary: The efficacy of MET-TKI monotherapy for NSCLC with MET exon 14 skipping mutations is unsatisfactory. Heterogeneity in co-occurring genetic alterations, rather than heterogeneity in MET exon 14 skipping mutation status, may affect the efficacy of MET-TKIs. Evaluating the therapeutic implications of intertumor and intratumor heterogeneity is important for future studies.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Fumiaki Takatsu, Hiromasa Yamamoto, Yasuaki Tomioka, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Katsuhito Takahashi, Shinichi Toyooka
Summary: This study retrospectively analyzed patients with retroperitoneal sarcoma metastasized to the lungs and found that age, disease-free interval, and size of metastasis were associated with prognosis. Pulmonary metastasectomy can be an effective management strategy for these patients.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Kei Namba, Ken Suzawa, Kazuhiko Shien, Akihiro Miura, Yuta Takahashi, Shunsaku Miyauchi, Kota Araki, Kentaro Nakata, Shuta Tomida, Shin Tanaka, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Junichi Soh, Masaomi Yamane, Shinichi Toyooka
Summary: This study demonstrates that the one-step nucleic acid amplification (OSNA) technique can be applied for intraoperative lymph node metastasis diagnosis in non-small cell lung cancer, with high sensitivity and specificity.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Kosuke Ochi, Ken Suzawa, Yin Min Thu, Fumiaki Takatsu, Shimpei Tsudaka, Yidan Zhu, Kentaro Nakata, Tatsuaki Takeda, Kazuhiko Shien, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Tadahiko Shien, Yoshiharu Okamoto, Shuta Tomida, Shinichi Toyooka
Summary: This study found that tranilast can inhibit the interaction between non-small cell lung cancer cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment, thereby reversing the drug resistance of cancer cells.
Article
Health Care Sciences & Services
Mikio Okazaki, Kazuhiko Shien, Ken Suzawa, Seiichiro Sugimoto, Shinichi Toyooka
Summary: This study describes the optimal position and port placement during robotic resection for various mediastinal tumors. The choice of approach should be based on the size, location, and aggressiveness of the tumor.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Surgery
Kento Fujii, Shin Tanaka, Megumi Ishihara, Kei Matsubara, Kohei Hashimoto, Shuji Okahara, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka
Summary: Living lung donors have a satisfactory long-term health-related quality of life after surgery, although some donors experience poorer physical, mental, and social health. Factors such as donor and recipient age, lung allocation score, and recipient death can affect the mental and social health of the donors. The study emphasizes the importance of informing potential donors about relevant risk factors and providing appropriate support for high-risk donors.
CLINICAL TRANSPLANTATION
(2023)
Article
Biotechnology & Applied Microbiology
Kentaro Nakata, Mikio Okazaki, Tomohisa Sakaue, Rie Kinoshita, Yuhei Komoda, Dai Shimizu, Haruchika Yamamoto, Shin Tanaka, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Hiromasa Yamamoto, Toshiaki Ohara, Seiichiro Sugimoto, Masaomi Yamane, Akihiro Matsukawa, Masakiyo Sakaguchi, Shinichi Toyooka
Summary: This study identified neutrophil-derived S100A8/A9 as a key factor in lung IR injury and identified it as a novel therapeutic target for lung IR injury. The use of anti-S100A8/A9 antibodies significantly improved IR injury.
BIOENGINEERING-BASEL
(2022)
Article
Oncology
Toshiya Fujiwara, Kazuhiko Shien, Motoki Matsuura, Junichi Soh, Hiromasa Yamamoto, Soshi Takao, Yuho Maki, Tsuyoshi Ueno, Ryujiro Sugimoto, Ken Suzawa, Mikio Okazaki, Hiroyuki Tao, Makio Hayama, Masafumi Kataoka, Yoshifumi Sano, Hidetoshi Inokawa, Motohiro Yamashita, Osamu Kawamata, Kazuhiko Kataoka, Shinichi Toyooka
Summary: This study found that surgical resection of primary tumors improved the prognosis of patients with non-small cell lung cancer (NSCLC) when pleural dissemination (PD) or malignant pleural effusion (MPE) existed, especially when the tumors harbored an EGFR mutation.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Kazuhiko Shien, Toshiya Fujiwara, Shinichi Toyooka
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Toshio Shiotani, Seiichiro Sugimoto, Yasuaki Tomioka, Haruchika Yamamoto, Shin Tanaka, Kentaroh Miyoshi, Ken Suzawa, Kazuhiko Shien, Hiromasa Yamamoto, Mikio Okazaki, Shinichi Toyooka
Summary: miR-21 in the bloodstream shows potential value in diagnosing CLAD after bilateral LT.
Editorial Material
Oncology
Toshiya Fujiwara, Kazuhiko Shien, Motoki Matsuura, Junichi Soh, Hiromasa Yamamoto, Soshi Takao, Yuho Maki, Tsuyoshi Ueno, Ryujiro Sugimoto, Ken Suzawa, Mikio Okazaki, Hiroyuki Tao, Makio Hayama, Masafumi Kataoka, Yoshifumi Sano, Hidetoshi Inokawa, Motohiro Yamashita, Osamu Kawamata, Kazuhiko Kataoka, Shinichi Toyooka
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Mikio Okazaki, Ken Suzawa, Kazuhiko Shien, Hiromasa Yamamoto, Kota Araki, Mototsugu Watanabe, Masanori Okada, Yuho Maki, Tsuyoshi Ueno, Shinji Otani, Ryujiro Sugimoto, Hitoshi Nishikawa, Riki Okita, Makio Hayama, Hiroyuki Tao, Toshiya Fujiwara, Hidetoshi Inokawa, Yuji Hirami, Yoshifumi Sano, Motohiro Yamashita, Osamu Kawamata, Motoki Matsuura, Shinichi Toyooka
Summary: We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database. The 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy, but with a higher frequency of intraoperative and postoperative complications.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2023)
Article
Cardiac & Cardiovascular Systems
Junichi Soh, Shinichi Toyooka, Yasushi Shintani, Jiro Okami, Hiroyuki Ito, Takashi Ohtsuka, Takeshi Morig, Shun-Ichi Watanabe, Hisao Asamura, Masayuki Chida, Shunsuke Endo, Ryoichi Nakanishi, Mitsutaka Kadokure, Hidemi Suzuki, Etsuo Miyaoka, Ichiro Yoshinon, And Hiroshi Date
Summary: This study investigated the prognostic validity of limited resection in patients with radiologically invasive lung cancer. The results showed that segmentectomy can have an equivalent prognosis to lobectomy in certain cases.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2022)
