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REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1449291
This article is part of the Research Topic Tumor-draining lymph nodes View all 3 articles

Lymphatic system regulation of anti-cancer immunity and metastasis

Provisionally accepted
Pin-Ji Lei Pin-Ji Lei 1Cameron Fraser Cameron Fraser 2Dennis Jones Dennis Jones 3Jessalyn M. Ubellacker Jessalyn M. Ubellacker 2Timothy P. Padera Timothy P. Padera 1*
  • 1 Massachusetts General Hospital, Harvard Medical School, Boston, United States
  • 2 Department of Molecular Metabolism, School of Public Health, Harvard University, Boston, Massachusetts, United States
  • 3 Department of Pathology and Laboratory Medicine, School of Medicine, Boston University, Boston, Massachusetts, United States

The final, formatted version of the article will be published soon.

    Cancer dissemination to lymph nodes (LN) is associated with a worse prognosis, increased incidence of distant metastases and reduced response to therapy. The LN microenvironment puts selective pressure on cancer cells, creating cells that can survive in LN as well as providing survival advantages for distant metastatic spread. Additionally, the presence of cancer cells leads to an immunosuppressive LN microenvironment, favoring the evasion of anti-cancer immune surveillance. However, recent studies have also characterized previously unrecognized roles for tumor-draining lymph nodes (TDLNs) in cancer immunotherapy response, including acting as a reservoir for pre-exhausted CD8+ T cells and stem-like CD8+ T cells. In this review, we will discuss the spread of cancer cells through the lymphatic system, the roles of TDLNs in metastasis and anticancer immune responses, and the therapeutic opportunities and challenges in targeting LN metastasis.

    Keywords: Lymphatics vessels, Lymph node metastasis, Tumor-draining lymph node (TDLN), Immunotharapy, cancer metastasis

    Received: 14 Jun 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Lei, Fraser, Jones, Ubellacker and Padera. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Timothy P. Padera, Massachusetts General Hospital, Harvard Medical School, Boston, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.