Cancer therapies utilizing antibodies to disrupt the PD-1/PD-L1 interaction have been among the most exciting developments in immunotherapy with Dr. James Allison and Dr. Tasuku Honjo receiving the Nobel Prize in Medicine this past week for their discovery of cancer therapy by inhibition of negative immune regulation.
This premise of this approach to cancer therapy is to harness the immune system to attack tumor cells by releasing a protein “brake” on the immune system. Cancer cells naturally express the protein PD-L1 on their cell surface indicating to the immune system that the cancerous cell is a part of the human body, i.e. “self”, rather than a foreign invader like a bacteria or virus, i.e. “non-self”. The PD-L1 molecule is also present on many non-cancerous cells to ensure that the immune system doesn’t target human cells. However, immunotherapy requires the immune system to target human cancerous cells. Some immunotherapy drugs use an antibody that blocks PD-L1 protection, allowing the body’s immune system to kill the cancer. These PD-L1 blockade therapies are effective for patients whose tumors test positive for PD-L1 but only ~15% of patients have lymphocyte-infiltrated, PD-L1-positive tumors.
Researchers at the University of Central Florida aimed to make PD-L1 therapies effective for more patients. PD-L1 expression on tumors is naturally induced by interferon-gamma (IFNγ), a cytokine secreted by natural killer cells. In the reported study, natural killer cells, stimulated with nanoparticles, attacked a tumor, secreted IFNγ, and induced the cancerous cells to present PD-L1, making it susceptible to PD-L1 blockade therapies. Combining NK cells with the an immunotherapy drug led to improved survival rates in mice implanted with ovarian cancer.
These results support the use of PD-1/PD-L1 immunotherapies in combination with NK cell therapy, which would broaden the pool of patients who could be clinically treated with these therapies.
The article titled “PD-L1 blockade enhances anti-tumor efficacy of NK cells” was published in OncoImmunology.