The lymph node microenvironment and its role in the progression of metastatic cancer

Abstract

Lymph nodes are initial sites for cancer metastasis in many solid tumors. However, their role in cancer progression is still not completely understood. Emerging evidence suggests that the lymph node microenvironment provides hospitable soil for the seeding and proliferation of cancer cells. Resident immune and stromal cells in the lymph node express and secrete molecules that may facilitate the survival of cancer cells in this organ. More comprehensive studies are warranted to fully understand the importance of the lymph node in tumor progression. Here, we will review the current knowledge of the role of the lymph node microenvironment in metastatic progression.

Keywords: Chemokine; Clonality; Lymph node; Lymphangiogenesis; Lymphatic vessels; Metastasis.

Figure 1

Alterations to tumor draining lymph nodes during cancer progression. A) Naïve lymph nodes are sites where foreign, pathogenic or self-antigens accumulate and adaptive immune responses are generated. Optimal interactions between antigen-loaded-dendritic cells and effector T lymphocytes in the lymph node stimulate effective immune responses that eliminate foreign and pathogenic antigens. B) Prior to cancer cell dissemination, tumor draining lymph nodes undergo many remodeling processes, including lymph node lymphangiogenesis, alterations in high endothelial venules, increases in chemokine and cytokine production and alterations in immune cell composition. These changes are thought to enable the growth of cancer cells that are seeded in the lymph node. C) Cancer bearing lymph nodes, undergo further changes, including the loss of high endothelial venules, regression of lymphangiogenic vessels, and impairment of lymphocyte recruitment. These changes inhibit adaptive immune responses and may enable the further spread of cancer cells to distant organs.