Same yet different — how lymph node heterogeneity affects immune responses

Lymph nodes are secondary lymphoid organs in which immune responses of the adaptive immune system are initiated and regulated. Distributed throughout the body and embedded in the lymphatic system, local lymph nodes are continuously informed about the state of the organs owing to a constant drainage of lymph. The tissue-derived lymph carries products of cell metabolism, proteins, carbohydrates, lipids, pathogens and circulating immune cells. Notably, there is a growing body of evidence that individual lymph nodes differ from each other in their capacity to generate immune responses. Here, we review the structure and function of the lymphatic system and then focus on the factors that lead to functional heterogeneity among different lymph nodes. We will discuss how lymph node heterogeneity impacts on cellular and humoral immune responses and the implications for vaccination, tumour development and tumour control by immunotherapy. This Review from Wolfgang Kastenmüller and colleagues highlights the heterogeneity that exists among lymph nodes at different anatomical locations. The authors consider the factors that contribute to lymph node heterogeneity and explain the relevance of this for the immune response, particularly in the contexts of vaccination and cancer.