Unleashing the therapeutic potential of tumor-draining lymph nodes: spotlight on bladder cancer.

Tumor-draining lymph nodes (TDLNs) are often involved during the metastasis of bladder cancer (BC), which is associated with a poor prognosis. Recent studies have shown that TDLNs are a major source of host anti-tumor immunity, which can impede tumor progression and favor tumor immunotherapy. However, during tumor progression, various tumor-derived mediators modulate the TDLN microenvironment, impairing their protective function. Ultimately, TDLNs provide the soil for the proliferation and dissemination of tumor cells. Therefore, surgical removal of TDLNs is commonly recommended in various solid tumors to prevent metastasis, but this poses significant challenges for leveraging TDLNs in immunotherapy. Additionally, lymph node dissection (LND) has not shown survival benefits in some tumors. Hence, the decision to remove TDLNs in oncological treatment needs to be reconsidered. Herein, we spotlight the TDLNs of BC and introduce how BC cells modulate stromal cells and immune cells to shape an immunosuppressive TDLN microenvironment for BC progression. We summarize the existing therapeutic strategies to reinvigorate anti-tumor immunity in TDLNs. Furthermore, we discuss whether to preserve TDLNs and the role of LND during oncological treatment.