A new study by researchers at UCLA Jonsson Comprehensive Cancer Center has identified a new combination therapy potentially to help overcome resistance to immunotherapy in people diagnosed with advanced lung cancer. The combined approach uses immune checkpoint inhibitors with ATRA, a safe drug that is widely used to treat leukemia. The team found that the combination therapy led to the eradication of over 70% of tumors when tested in mice with LKB1-deficient lung cancer. It also generated lasting tumor specific immunity.
Immune checkpoint inhibitors have dramatically improved outcomes for people with lung cancer. The five-year survival rate of patients with advanced disease receiving this treatment is over 13% compared to 5% in patients receiving conventional chemotherapy. Although immunotherapy has been successful for many patients, the majority of patients still do not respond to therapy.
To help increase the number of patients who benefit from this therapy, the researchers sought to identify the mechanisms of resistance to treatment. The LKB1 tumor suppressor gene is mutated in 20% of patients with non-small cell lung cancer and 30% of KRAS mutant non-small cell lung cancer. It is also a major gene associated with resistance to immune checkpoint inhibitors. By identifying the aberrant pathways caused by the LKB1 mutation, researchers are discovering a new therapy that targets the pathway and sensitizes LKB1-deficient tumors to immunotherapy.
To assess the response of the combination therapy, the researchers tested the therapy in mice that were injected with LKB1-deficient lung tumors.
The study provides evidence that the use of ATRA in combination with checkpoint inhibitors could potentially help patients with advanced lung cancer with an LKB1 mutation to have a positive response to LKB1. immunotherapy.
University of California, Los Angeles (UCLA), Health Sciences
Li, R., et al. (2021) Inhibition of myeloid-derived granulocytic suppressor cells overcomes resistance to immune checkpoint inhibition in LKB1-deficient non-small cell lung cancer. Research against cancer. doi.org/10.1158/0008-5472.CAN-20-3564.