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Lymph node colonization induces tumor-immune tolerance to promote distant metastasis.
Reticker-Flynn, Nathan E; Zhang, Weiruo; Belk, Julia A; Basto, Pamela A; Escalante, Nichole K; Pilarowski, Genay O W; Bejnood, Alborz; Martins, Maria M; Kenkel, Justin A; Linde, Ian L; Bagchi, Sreya; Yuan, Robert; Chang, Serena; Spitzer, Matthew H; Carmi, Yaron; Cheng, Jiahan; Tolentino, Lorna L; Choi, Okmi; Wu, Nancy; Kong, Christina S; Gentles, Andrew J; Sunwoo, John B; Satpathy, Ansuman T; Plevritis, Sylvia K; Engleman, Edgar G.
Affiliation
  • Reticker-Flynn NE; Department of Pathology, Stanford University, Stanford, CA 94305, USA. Electronic address: retickerflynn@stanford.edu.
  • Zhang W; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA.
  • Belk JA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Basto PA; Division of Oncology, Department of Medicine, Stanford University, Palo Alto, CA 94305, USA.
  • Escalante NK; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Pilarowski GOW; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Bejnood A; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA.
  • Martins MM; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Kenkel JA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Linde IL; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Bagchi S; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Yuan R; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Chang S; Institute for Immunity, Transplantation, and Infection Operations, Stanford University, Palo Alto, CA 94305, USA; Department of Otolaryngology-Head & Neck Surgery, Stanford University, Palo Alto, CA 94305, USA.
  • Spitzer MH; Department of Microbiology and Immunology and Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, CA, USA.
  • Carmi Y; Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Cheng J; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Tolentino LL; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Choi O; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Wu N; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Kong CS; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University, Palo Alto, CA 94305, USA.
  • Gentles AJ; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Stanford University, Palo Alto, CA 94305, USA.
  • Sunwoo JB; Department of Otolaryngology-Head & Neck Surgery, Stanford University, Palo Alto, CA 94305, USA; Stanford Cancer Institute, Stanford University, Palo Alto, CA 94305, USA.
  • Satpathy AT; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University, Palo Alto, CA 94305, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Plevritis SK; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA; Department of Radiology, Stanford University, Palo Alto, CA 94305, USA.
  • Engleman EG; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University, Palo Alto, CA 94305, USA. Electronic address: edgareng@stanford.edu.
Cell ; 185(11): 1924-1942.e23, 2022 05 26.
Article de En | MEDLINE | ID: mdl-35525247
ABSTRACT
For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its utility as a biomarker, whether and how LN metastasis plays an active role in shaping distant metastasis remains an open question. Here, we develop a syngeneic melanoma mouse model of LN metastasis to investigate how tumors spread to LNs and whether LN colonization influences metastasis to distant tissues. We show that an epigenetically instilled tumor-intrinsic interferon response program confers enhanced LN metastatic potential by enabling the evasion of NK cells and promoting LN colonization. LN metastases resist T cell-mediated cytotoxicity, induce antigen-specific regulatory T cells, and generate tumor-specific immune tolerance that subsequently facilitates distant tumor colonization. These effects extend to human cancers and other murine cancer models, implicating a conserved systemic mechanism by which malignancies spread to distant organs.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Noeuds lymphatiques / Mélanome Type d'étude: Prognostic_studies Limites: Animals Langue: En Journal: Cell Année: 2022 Type de document: Article
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Noeuds lymphatiques / Mélanome Type d'étude: Prognostic_studies Limites: Animals Langue: En Journal: Cell Année: 2022 Type de document: Article