Thus, drawing from the trends that we have summarized here, it can be projected that there will be a continuous emergence of strategies that utilize other tumor-specific targets in combination with 4-1BB agonism with the goal of localizing the immune stimulatory and anti-tumor effects of 4-1BB signaling to the tumor while minimizing off-target, peripheral 4-1BB activation. The gene discussed is TNFRSF9; the disease is neoplasm.