Immune Checkpoint Blockade Activates Macrophages and Remodels the Lymph Node Microenvironment in Melanoma Metastasis

Activation of lymph node immune cells can promote effective immune checkpoint blockade responses or alternately enforce immunosuppression. Here we investigated a murine model of lymph node melanoma metastasis that was amenable to combination immune checkpoint blockade at the cellular, protein, and transcriptional level.

Checkpoint blockade spatially reorganized and activated T and B lymphocytes as well as lymph node stromal cells. Notably, myeloid cells, key mediators of lymph node immune function, were reprogrammed to an immunostimulatory phenotype upon checkpoint blockade. Our data supports a model in which immunostimulatory macrophages are induced and macrophage-mediated T cell suppression is released during effective immunotherapy.