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Lymph node colonization induces tumor-immune tolerance to promote distant metastasis.
- Source :
-
Cell [Cell] 2022 May 26; Vol. 185 (11), pp. 1924-1942.e23. Date of Electronic Publication: 2022 May 06. - Publication Year :
- 2022
-
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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2022 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 185
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 35525247
- Full Text :
- https://doi.org/10.1016/j.cell.2022.04.019