Abstract / Summary
The factors that drive therapeutic resistance and variable patient response to immune checkpoint blockade therapies within the metastatic lymph nodes are poorly understood. Activation of lymph node immune cells is associated with effective immune checkpoint blockade responses or alternately enforce immunosuppression. Here we investigate a murine model of lymph node melanoma metastasis that is amenable to combination immune checkpoint blockade at the cellular, protein, and transcriptional level. Checkpoint blockade spatially reorganizes and activates T and B lymphocytes as well as lymph node stromal cells. Notably, myeloid cells, key mediators of lymph node immune function, are reprogrammed to an immunostimulatory phenotype upon checkpoint blockade. Our findings in this murine lymph node metastasis system support a model in which immunostimulatory macrophages are induced and macrophage-mediated T cell suppression is released during effective immunotherapy.