In tumor cells that are resistant to immunotherapy with checkpoint inhibitors, radiotherapy and chemotherapy can synergize with a specific immunotherapy combination to induce tumor cell death. The checkpoint inhibitor (red Y) 'removes the brake' on the immune cells (T cells) and the other form of immunotherapy (an antibody to CD137, green Y) 'presses the gas pedal' on the immune cell. Radiotherapy and chemotherapy enable the activated immune cells to kill the tumor cells (shriveled purple cells).
Indeed, the combination of these four treatment modalities proved to be very efficient in mice. The newly raised immune cells did a better job and the mice survived longer. The immune cells even cleared tumor cells that resided outside the irradiated tissue. In the future, chemo-radio-immunotherapy may contribute to improving the survival of patients with tumors that do not respond well to immunotherapy with checkpoint inhibitors.
Researchers of the Netherlands Cancer Institute are already studying this concept in several patient cohorts. The PEMBRO-RT trial combines radiotherapy with checkpoint inhibition in patients with lung cancer. The TONIC-trial investigates to what extend radiotherapy and chemotherapy can improve the efficacy of checkpoint inhibitors in breast cancer patients.
Read the scientific article here.
This research was financed by the Dutch Cancer Society and Health Holland.