The body's immune system is the first line of defense against the development of cancerous cells, notes Louis M. Weiner, MD. However, many tumors overcome this defense mechanism by expressing immune checkpoints, which prevents antitumor T cell activation. However, the blockade of these checkpoints, specifically PD-1, PD-L1, and CTLA-4, allows the immune system to recognize the cancer cells, causing an immune response. Moreover, this method could be adapted across all tumors, since other immune checkpoints exist, believes Weiner.

At this point, it appears that tumors with a large mutation burden are the most immunogenic, notes Roy S. Herbst, MD. More research is still needed, not only focused on the checkpoints themselves but also on the T cells that they activate. To this point, Weiner notes that research has focused on the modification and amplification of T cells. These approaches could be used in combination with the checkpoint inhibitors, since they appear to have complimentary mechanisms, believes Weiner.

The next step will be the exploration of combinatorial therapies, notes Robert Dreicer, MD. Non-muscle invasive bladder cancer represents an unmet need therapeutically and economically, as one of the most expensive diseases to treat. Strategies that combine an intravesical immunomodulatory therapy like BCG with a systemic therapy for patients with bladder cancer are very interesting and important, Dreicer believes. The next step for immunotherapy research will focus on combinations.