Fig.1.

Rationale to prime the immune system with PD-1 blockade prior to nephrectomy. At baseline, it is thought that there is an ongoing but ineffective inflammatory T cell response against the primary tumor. Preclinical work suggests PD-1 blockade may induce proliferation of anti-tumor T cells in the tumor, tumor microenvironment, and lymph nodes supporting the tumor. These antigen specific T cells can then traffic to distant sites through the lymphatic and circulatory system where they can eliminate metastatic disease. They can transform to memory cells capable of continual suppression or elimination of metastatic disease or new primaries. Removal of the kidney tumor by nephrectomy before priming would eliminate the majority of tumor antigen as well as nearby effector cells, which produce the necessary immunomodulatory cytokines, and could result in a less potent response to adjuvant PD-1 pathway blockade alone.