Figure 1.

Cellular changes in lymph nodes associated with breast cancer metastases. A: Graphical representation of a normal lymph node. The subcapsular sinus (brown) contains macrophages and is lined by lymphatic endothelial cells. The cortex (blue) contains follicles that consist of B cells and follicular dendritic cells. Fibroblastic reticular cells/conduits are depicted in the cortex and paracortex (green). The paracortex contains T cells, dendritic cells, and high endothelial venules. Macrophages are depicted in the medulla (purple). B: Enlargement of tumor-involved lymph node is seen with the invasion and growth of cancer cells. B cells accumulate in tumor-involved lymph nodes (germinal centers are depicted as darker blue), whereas the overall T cell compartment contracts. Of note, the regulatory T cell population has been shown to expand in tumor-involved lymph nodes. Remodeling of lymph nodes and enhanced collagen production by fibroblastic reticular cells and recruited cancer-associated fibroblasts have been observed in tumor-involved lymph nodes. High endothelial venules are remodeled and show an increased lumen diameter and thinner endothelial layer. In tumor-involved lymph nodes, the lymphatic vasculature is expanded, many dendritic cells are immature, and subsets of functionally impaired natural killer cells and T cells are present. Macrophages, neutrophils,⁸ and myeloid-derived suppressor cells are recruited to tumor-involved lymph nodes and exhibit a protumor phenotype. Cancer cells can gain access to lymphatic and blood vasculatures of lymph nodes to further metastasize.