Guardians of immunity: the role of tumour-draining lymph node in cancer immunity

The success of immunotherapies in cancer has changed the landscape of cancer research. The tumour-draining lymph node (TDLN) is emerging as an organ specific target to enhance the efficacy and minimize the toxicity of immunotherapies; this approach is based on the TDLN being the first lymph node to encounter metastatic tumour cells and various tumour-derived factors. Both anti-tumour and immunosuppressive T cells can originate from the TDLNs. Accumulating evidence has shown that immunosuppressive T cells are activated in the TDLN before migrating to the tumour to perform their functions. This suggests that targeting the TDLN could be crucial for intercepting immunosuppressive T cells and enhancing immunotherapy. Notably, regional delivery of ICI drugs to the TDLN has been shown to achieve similar outcomes to systemic delivery but with reduced toxicity to the host. T cell immunity is well-known to be regulated by dendritic cells (DCs) in cancer. However, B cells, which form a significant population of immune cells in the TDLNs, have emerging roles in this regulation. This review seeks to elucidate the mechanisms of cancer immunity within the TDLN and to explore the potential role of B cells in immunotherapies.