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Molecular subtypes of lung adenocarcinoma present distinct immune tumor microenvironments.
Fukuda, Hironori; Arai, Kosuke; Mizuno, Hideaki; Nishito, Yukari; Motoi, Noriko; Arai, Yasuhito; Hiraoka, Nobuyoshi; Shibata, Tatsuhiro; Sonobe, Yukiko; Kayukawa, Yoko; Hashimoto, Eri; Takahashi, Mina; Fujii, Etsuko; Maruyama, Toru; Kuwabara, Kenta; Nishizawa, Takashi; Mizoguchi, Yukihiro; Yoshida, Yukihiro; Watanabe, Shun-Ichi; Yamashita, Makiko; Kitano, Shigehisa; Sakamoto, Hiromi; Nagata, Yuki; Mitsumori, Risa; Ozaki, Kouichi; Niida, Shumpei; Kanai, Yae; Hirayama, Akiyoshi; Soga, Tomoyoshi; Tsukada, Keisuke; Yabuki, Nami; Shimada, Mei; Kitazawa, Takehisa; Natori, Osamu; Sawada, Noriaki; Kato, Atsuhiko; Yoshida, Teruhiko; Yasuda, Kazuki; Ochiai, Atsushi; Tsunoda, Hiroyuki; Aoki, Kazunori.
Afiliação
  • Fukuda H; Department of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.
  • Arai K; Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
  • Mizuno H; Department of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.
  • Nishito Y; Department of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • Motoi N; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Arai Y; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Hiraoka N; Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
  • Shibata T; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Sonobe Y; Department of Analytical Pathology, National Cancer Center Research Institute, Tokyo, Japan.
  • Kayukawa Y; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Hashimoto E; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Takahashi M; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Fujii E; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Maruyama T; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Kuwabara K; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Nishizawa T; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Mizoguchi Y; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Yoshida Y; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Watanabe SI; Department of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.
  • Yamashita M; Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
  • Kitano S; Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
  • Sakamoto H; Advanced Medical Development Center, Cancer Research Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • Nagata Y; Advanced Medical Development Center, Cancer Research Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • Mitsumori R; Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan.
  • Ozaki K; Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.
  • Niida S; Bioresource Research Center, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.
  • Kanai Y; Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.
  • Hirayama A; Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.
  • Soga T; Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.
  • Tsukada K; Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
  • Yabuki N; Institute for Advanced Biosciences, Keio University, Yamagata, Japan.
  • Shimada M; Institute for Advanced Biosciences, Keio University, Yamagata, Japan.
  • Kitazawa T; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Natori O; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Sawada N; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Kato A; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Yoshida T; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Yasuda K; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Ochiai A; Chugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
  • Tsunoda H; Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.
  • Aoki K; Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Cancer Sci ; 115(6): 1763-1777, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38527308
ABSTRACT
Overcoming resistance to immune checkpoint inhibitors is an important issue in patients with non-small-cell lung cancer (NSCLC). Transcriptome analysis shows that adenocarcinoma can be divided into three molecular subtypes terminal respiratory unit (TRU), proximal proliferative (PP), and proximal inflammatory (PI), and squamous cell carcinoma (LUSQ) into four. However, the immunological characteristics of these subtypes are not fully understood. In this study, we investigated the immune landscape of NSCLC tissues in molecular subtypes using a multi-omics dataset, including tumor-infiltrating leukocytes (TILs) analyzed using flow cytometry, RNA sequences, whole exome sequences, metabolomic analysis, and clinicopathologic findings. In the PI subtype, the number of TILs increased and the immune response in the tumor microenvironment (TME) was activated, as indicated by high levels of tertiary lymphoid structures, and high cytotoxic marker levels. Patient prognosis was worse in the PP subtype than in other adenocarcinoma subtypes. Glucose transporter 1 (GLUT1) expression levels were upregulated and lactate accumulated in the TME of the PP subtype. This could lead to the formation of an immunosuppressive TME, including the inactivation of antigen-presenting cells. The TRU subtype had low biological malignancy and "cold" tumor-immune phenotypes. Squamous cell carcinoma (LUSQ) did not show distinct immunological characteristics in its respective subtypes. Elucidation of the immune characteristics of molecular subtypes could lead to the development of personalized immune therapy for lung cancer. Immune checkpoint inhibitors could be an effective treatment for the PI subtype. Glycolysis is a potential target for converting an immunosuppressive TME into an antitumorigenic TME in the PP subtype.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos do Interstício Tumoral / Transportador de Glucose Tipo 1 / Microambiente Tumoral / Adenocarcinoma de Pulmão / Neoplasias Pulmonares Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos do Interstício Tumoral / Transportador de Glucose Tipo 1 / Microambiente Tumoral / Adenocarcinoma de Pulmão / Neoplasias Pulmonares Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article