Intra- and peritumoral lymphatics and tumor-draining lymph nodes play major roles in mediating the adaptive immune response to cancer immunotherapy. Despite this, current paradigms of clinical cancer management seldom seek to therapeutically modulate tumor-lymphatic immune crosstalk. This review explores recent developments that set the stage for how this regulatory axis can be therapeutically manipulated, with a particular emphasis on tumor-localized immunomodulation. Building on this idea, the nature of tumor-lymphatic immune crosstalk and relevant immunotherapeutic targets and pathways are reviewed, with a focus on their translational potential. Engineered drug delivery systems that enhance intratumoral immunotherapy by improving drug delivery to both the tumor and lymph nodes are also highlighted.
Keywords: cancer immunotherapy; drug delivery; immune crosstalk; lymphatics; sentinel lymph node.