Radiation therapy is commonly used to reduce tumor size and improve symptoms of non-small cell lung cancer. While initially beneficial, many patients will eventually relapse with metastatic tumors. Last year, two immunotherapies that improve anti-tumor T cell responses by inhibiting the PD-1 pathway were approved for non-small cell lung carcinoma. However, it is not yet known if combining immunotherapy with traditional radiation therapy will improve outcome for lung cancer patients. In this issue of JCI Insight, researchers from the NYU Langone Medical Center and the Dana Farber Cancer Institute used a genetically engineered mouse model of non-small cell lung cancer to examine the efficacy of treatment with radiotherapy and a PD-1 inhibitory antibody. The research group, led by Alec Kimmelman and Kwok-Kin Wong, showed that combination therapy improved survival when used as an initial therapeutic approach. However, using anti-PD1 therapy for tumors that had relapsed after radiation therapy showed no benefits. In addition, tumors that lost expression of the tumor suppressor Stk11/Lkb1 (serine/threonine kinase 11/liver kinase B1), which is mutated in approximately 20% of non-small cell lung cancers, did not benefit from combination therapy. These murine lung cancer model findings may help guide future translational studies examining combination radiotherapy and checkpoint blockade.
Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer
Alec C. Kimmelman
NYU Langone Medical Center
Dana Farber Cancer Institute
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