Lymph node colonization induces tumor-immune tolerance to promote distant metastasis
Menée à l'aide de lignées cellulaires, d'un modèle murin de mélanome et d'échantillons tumoraux prélevés sur des patients atteints d'un carcinome épidermoïde de la tête et du cou, cette étude met en évidence un mécanisme par lequel la colonisation des ganglions lymphatiques par les cellules cancéreuses favorise le développement de métastases distantes en générant une tolérance immunitaire vis-à-vis de la tumeur
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.