The pre-metastatic niche in lymph nodes: formation and characteristics

Lymph node metastasis is a crucial prognostic parameter in many different types of cancers and a gateway for further dissemination to distant organs. Prior to metastatic dissemination, the primary tumor prepares for the remodeling of the draining (sentinel) lymph node by secreting soluble factors or releasing extracellular vesicles that are transported by lymphatic vessels. These important changes occur before the appearance of the first metastatic cell and create what is known as a pre-metastatic niche giving rise to the subsequent survival and growth of metastatic cells. In this review, the lymph node structure, matrix composition and the emerging heterogeneity of cells forming it are described. Current knowledge of the major cellular and molecular processes associated with nodal pre-metastatic niche formation, including lymphangiogenesis, extracellular matrix remodeling, and immunosuppressive cell enlisting in lymph nodes are additionally summarized. Finally, future directions that research could possibly take and the clinical impact are discussed.

Automated summary

Lymph node metastasis is a significant prognostic factor in various cancers, serving as a gateway for further dissemination. Prior to metastasis, the primary tumor reshapes the draining lymph node by secreting soluble factors or releasing extracellular vesicles, creating a pre-metastatic niche for the survival and growth of metastatic cells. This review highlights the structure of lymph nodes, matrix composition, cellular heterogeneity, and major processes associated with nodal pre-metastatic niche formation, offering insights into potential research directions and clinical implications.