Tumor-draining lymph nodes: At the crossroads of metastasis and immunity

Early engagement of the lymphatic system by solid tumors in peripheral, nonlymphoid tissues is a clinical hallmark of cancer and often forecasts poor prognosis. The significance of lymph node metastasis for distant spread, however, has been questioned by large-scale lymph node dissection trials and the likely prevalence of direct hematogenous metastasis. Still, an emerging appreciation for the immunological role of the tumor-draining lymph node has renewed interest in its basic biology, role in metastatic progression, antitumor immunity, and patient outcomes. In this review, we discuss our current understanding of the early mechanisms through which tumors engage lymphatic transport and condition tumor-draining lymph nodes, the significance of these changes for both metastasis and immunity, and potential implications of the tumor-draining lymph node for immunotherapy.