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Lymphatics, lymph nodes and the immune system: barriers and gateways for cancer spread

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Abstract

Metastasis to the regional lymph node is the most important prognostic indicator for the outcomes of patients with sold cancer. In general, it is well recognized that cancer development is genetically determined with progression from the microenvironment of the primary tumor site, oftentimes via the SLN gateway, to the distant sites. In about 20 % of the time, the cancer cells may spread directly through the blood vascular system to the distant sites. Thus, in general, cancer progression is consistent with Hellman’s spectrum theory in that development of nodal and systemic metastasis from a localized cancer growth is a progressive process. Cancer proliferation within the tumor microenvironment may give rise to increased tumor heterogeneity, which is further complicated by its continuous change through its evolution within the host in a Darwinian sense. It is crucial to understand the molecular process of lymphangiogenesis and hemangiogenesis in the tumor microenvironment with respect to the initial steps of cancer cells entering into the lymphatic and vascular systems so that rational therapy can be developed to curb the process of specific routes of metastasis. This chapter elucidates the role of lymphatics, nodal metastasis and antitumor immunity. We present novel immune targets in nodal metastases, the importance of the lymph node as a pre-metastatic niche, and immune-related proteins as biomarkers of metastasis.

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Authors and Affiliations

  1. Melanoma Program Center for Melanoma Research and Treatment, San Francisco, CA, USA

    Stanley P. L. Leong

  2. California Pacific Medical Center Research institute, San Francisco, CA, USA

    Stanley P. L. Leong

  3. University of California, San Francisco School of Medicine 2340 Clay Street, 2nd Floor, San Francisco, CA, 94115, USA

    Stanley P. L. Leong

  4. Hillman Cancer Center Research, Pavilion 5117 Centre Avenue, Room 2.26b, Pittsburgh, PA, 15213, USA

    Robert L. Ferris

  5. John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA, 90404, USA

    David S. B. Hoon & Donald L. Morton

  6. University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA

    Michael T. Lotze

  7. Translational Research Molecular Medicine Institute, 100 Technology Drive, Pittsburgh, PA, 15219, USA

    Michael T. Lotze

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  1. Robert L. Ferris
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  2. Michael T. Lotze
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  3. Stanley P. L. Leong
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  4. David S. B. Hoon
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  5. Donald L. Morton
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Correspondence to Robert L. Ferris.

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Ferris, R.L., Lotze, M.T., Leong, S.P.L. et al. Lymphatics, lymph nodes and the immune system: barriers and gateways for cancer spread. Clin Exp Metastasis 29, 729–736 (2012). https://doi.org/10.1007/s10585-012-9520-2

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  • DOI: https://doi.org/10.1007/s10585-012-9520-2

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