| First Author | Reticker-Flynn NE | Year | 2022 |
| Journal | Cell | Volume | 185 |
| Issue | 11 | Pages | 1924-1942.e23 |
| PubMed ID | 35525247 | Mgi Jnum | J:324929 |
| Mgi Id | MGI:7281643 | Doi | 10.1016/j.cell.2022.04.019 |
| Citation | Reticker-Flynn NE, et al. (2022) Lymph node colonization induces tumor-immune tolerance to promote distant metastasis. Cell 185(11):1924-1942.e23 |
| abstractText | 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. |
