Tumor-Derived TGFβ-1 Induces Dendritic Cell Apoptosis in the Sentinel Lymph Node

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  • Manabu Ito
    Division of Thoracic Surgery, Department of Surgery, Akita University School of Medicine , Hondo Akita City ,
  • Yoshihiro Minamiya
    Division of Thoracic Surgery, Department of Surgery, Akita University School of Medicine , Hondo Akita City ,
  • Hideki Kawai
    Division of Thoracic Surgery, Department of Surgery, Akita University School of Medicine , Hondo Akita City ,
  • Satoshi Saito
    Division of Thoracic Surgery, Department of Surgery, Akita University School of Medicine , Hondo Akita City ,
  • Hajime Saito
    Division of Thoracic Surgery, Department of Surgery, Akita University School of Medicine , Hondo Akita City ,
  • Taku Nakagawa
    Division of Thoracic Surgery, Department of Surgery, Akita University School of Medicine , Hondo Akita City ,
  • Kazuhiro Imai
    Division of Thoracic Surgery, Department of Surgery, Akita University School of Medicine , Hondo Akita City ,
  • Makoto Hirokawa
    Division of Hematology and Oncology, Department of Medicine, Akita University School of Medicine , Hondo Akita City ,
  • Jun-ichi Ogawa
    Division of Thoracic Surgery, Department of Surgery, Akita University School of Medicine , Hondo Akita City ,

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公開日
2006-05-01
権利情報
  • https://academic.oup.com/pages/standard-publication-reuse-rights
DOI
  • 10.4049/jimmunol.176.9.5637
公開者
Oxford University Press (OUP)

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<jats:title>Abstract</jats:title> <jats:p>Lymphatic flux from a primary tumor initially flows into a tumor-draining lymph node (LN), the so-called sentinel LN (SLN). Carried by the lymph fluid are a variety of mediators produced by the tumor that can influence immune responses within the SLN, making it a good model with which to investigate tumor-related immunology. For instance, dendritic cell (DC) numbers are reduced in SLNs from melanoma and breast cancer patients. In the present study, we investigated the mechanism by which DC numbers were reduced within SLNs from patients with non-small cell lung cancer. We found that the incidence of apoptosis among DCs was higher in SLNs than in non-SLNs, as were levels of TGFβ-1. In contrast, levels of TGFβ-1 mRNA did not differ between SLNs and non-SLNs, but were 30 times higher in tumors than in either LN type. In vitro, incubation for 2 days with TGFβ-1 induced apoptosis among both cultured DCs and DCs acutely isolated from normal thoracic LNs, effects that were blocked by the TGFβ-1 inhibitor DAN/Fc chimera. Taken together, these results suggest that tumor-derived TGFβ-1 induces immunosuppression within SLNs before the movement of tumor cells into the SLNs, thereby facilitating metastasis within those nodes.</jats:p>

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