Cancer Immunotherapy in the Clinic
Since the FDA approval of several immunotherapeutic checkpoint inhibitors in the last few years, immune therapies in the advanced, metastatic setting as well as in the upfront setting of a variety of solid tumors have emerged. With additional agents in clinical trials and on the developmental horizon, an increasing number of studies aim to elucidate the role of traditional cytotoxic cancer therapies including radiation therapy and its interaction with these various immune modulating agents. A number of preclinical studies with clinical correlation have demonstrated that radiation therapy (delivered using a hypofractionated regimen) can synergize with anti-CTLA-4 antibody and induce complete abscopal responses, partial responses or stable disease, as observed in a subset of patients treated with ipilimumab for metastatic melanoma and metastatic non-small cell lung cancer, respectively (Figure 3).4-6 A similar phenomenon of improved antitumor response has been observed in preclinical models combining radiation with blockade of PD-1 or PD-L1, with improvement in survival noted with the addition of anti-PD-1 antibody to single dose radiation in mice with intracranial glioma, and improved response observed in colorectal tumors with upregulated PD-L1 treated with PD-L1 blockade.3 Multifactorial combination approaches to enhance antitumor response leading to tumor rejection and prevention of T-cell exhaustion are under investigation, and may prove to be the most promising strategy to harnessing the benefits of cancer immunotherapy.
With ever emerging data and clinical trials underway, the time is ripe for an in-depth evaluation of the landscape of radiation and cancer immunotherapy, setting the stage to pose critical questions which will define the direction of clinical trials and ultimately, future clinical practice.
Used with permission from Macmillan Publishers Ltd: Nature, 520 (7547): 373-77, copyright 2015.
