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Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer.
Imamura, Kosuke; Tomita, Yusuke; Sato, Ryo; Ikeda, Tokunori; Iyama, Shinji; Jodai, Takayuki; Takahashi, Misako; Takaki, Akira; Akaike, Kimitaka; Hamada, Shohei; Sakata, Shinya; Saruwatari, Koichi; Saeki, Sho; Ikeda, Koei; Suzuki, Makoto; Sakagami, Takuro.
Afiliación
  • Imamura K; Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Tomita Y; Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Sato R; Laboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
  • Ikeda T; Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1, Ikeda Nishi-ku, Kumamoto-shi 860-0082, Kumamoto, Japan.
  • Iyama S; Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Jodai T; Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Takahashi M; Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Takaki A; Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Akaike K; Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Hamada S; Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Sakata S; Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Saruwatari K; Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Saeki S; Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Ikeda K; Department of Thoracic and Breast Surgery, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Suzuki M; Department of Thoracic and Breast Surgery, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
  • Sakagami T; Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-shi 860-8556, Kumamoto, Japan.
Int J Mol Sci ; 23(22)2022 Nov 08.
Article en En | MEDLINE | ID: mdl-36430217
T cells express an actin-binding protein, drebrin, which is recruited to the contact site between the T cells and antigen-presenting cells during the formation of immunological synapses. However, little is known about the clinical implications of drebrin-expressing, tumor-infiltrating lymphocytes (TILs). To address this issue, we evaluated 34 surgical specimens of pathological stage I-IIIA squamous cell lung cancer. The immune context of primary tumors was investigated using fluorescent multiplex immunohistochemistry. The high-speed scanning of whole-slide images was performed, and the tissue localization of TILs in the tumor cell nest and surrounding stroma was automatically profiled and quantified. Drebrin-expressing T cells were characterized using drebrin+ T cells induced in vitro and publicly available single-cell RNA sequence (scRNA-seq) database. Survival analysis using the propensity scores revealed that a high infiltration of drebrin+ TILs within the tumor cell nest was independently associated with short relapse-free survival and overall survival. Drebrin+ T cells induced in vitro co-expressed multiple exhaustion-associated molecules. The scRNA-seq analyses confirmed that the exhausted tumor-infiltrating CD8+ T cells specifically expressed drebrin. Our study suggests that drebrin-expressing T cells present an exhausted phenotype and that tumor-infiltrating drebrin+ T cells affect clinical outcomes in patients with resectable squamous cell lung cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuropéptidos / Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuropéptidos / Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza