Boosting Response: The Impact of Immune Checkpoint Inhibitors on Radiation Treatment Schedules

Firas Mourtada and Jennifer Sims-Mourtada*

Boosting Response: The Impact of Immune Checkpoint Inhibitors on Radiation Treatment Schedules. The recent FDA approvals of immunomodulatory drugs such as Nivoluvamab, Pembrolizumab and Ipilimumab for treatment of Non-small cell lung cancer and melanoma have renewed interest in cancer immunotherapy. Initial attempts to activate the immune system to improve anti-tumor immunity by vaccination and/or cytokine treatments failed due to low response rates and high toxicity.

However, improved knowledge of interactions between tumor cells and the immune system has led to a change in strategy. Recently, it has been shown that tumors activate immune checkpoint pathways which suppress any anti-tumor immune responses. Immune checkpoint inhibitors block these pathways and can evoke the power of cytotoxic CD8+ T lymphocytes to eliminate cancer cells.

The first immune checkpoint inhibitor Ipilimumab, a monoclonal antibody to CTLA-4, was approved by the US FDA in 2011 for the treatment of unresectable or metastatic melanoma and has since shown some efficacy for the treatment of other solid tumors such as lung, head and neck, and sarcomas in combination with standard treatment regimens.

CTLA-4 is a surface receptor which inhibits T-cell co-stimulatory signals and prevents cytotoxic T-cell activation. By blocking CTLA-4 signaling, ipilimumab allows activation of anti-tumor CD8+ T-cell responses. The success of ipilimumab led the way for development of other immune checkpoint inhibitors such as Nivoluvamab and Pembrolizumab which both target the PD-1 pathway.

Blocking the PD-1 pathway results in increased activation of effector T cells and increased tumor immunity. In spite of promising results with these new immunotherapies, many patients do not respond or develop resistance.

Cancer Stud Mol Med Open J. 2015; 2(2): e8-e10. doi: 10.17140/CSMMOJ-2-e002