Covid-19 Vaccines Enhance the Effectiveness of Immune Checkpoint Inhibitors in Fighting Cancer
Covid-19 Vaccines Enhance the Effectiveness of Immune Checkpoint Inhibitors in Fighting Cancer
Steven J. Madore, PhD (ICBR Associate Director for Science, UFHCI Associate Director for Shared Resources)
Tumor cells fend off the attacks of immune system T-cells by expressing proteins like PD-L1 on their cell surface. The PD-L1 on the surface of the tumor cell binds to a T-cell surface receptor protein called PD-1 and silences the killing action of the T-cells. Blocking the binding of PD-L1 to PD-1 with a monoclonal antibody drug called an immune checkpoint inhibitor (ICI; like anti-PD-L1 or anti-PD-1) allows the T-cells to kill tumor cells. Essentially ICIs act as brakes on the immune system and enable T-cells to recognize and attack cancer cells more effectively.
Although ICIs substantially improve survival in some patients, most patients do not benefit from these therapies. The poor response can be attributed to the tumor “microenvironment” (TME) –a complex ecosystem that surrounds the tumor tissue consisting of blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix. Cancer cells interact with various components of the TME to enhance cancer cell growth and promote invasion into healthy tissues. Cancer cells can influence the TME by releasing extracellular signals that enhance tumor blood flow and silence the normal immune response. There are currently no clinically available methods to improve responses to ICI by modifying the TME.
In a study published in the high impact journal Nature, UF physician scientist Dr. Elias Sayour (Professor, Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute) and colleagues, along with investigators at the University of Texas MD Anderson Cancer Center, reported that cancer patients undergoing treatment with ICI who received the COVID-19 mRNA vaccine showed a significant increase in survival times. Adam J. Grippin, PhD from the Department of Radiation Oncology at University of Texas MD Anderson Cancer Center was the lead author for this publication.
Dr. Sayour and colleagues showed that patients who received the SARS-CoV-2 mRNA vaccine within 100 days of initiating treatment with ICIs showed significantly improved median and three-year overall survival. This effect could also be replicated in a mouse model of human cancer. These results demonstrate that clinically available mRNA vaccines targeting non-tumor-related antigens are potent immune modulators capable of sensitizing tumors to ICIs drug treatment.
This important research study was supported by the ICBR Cytometry and Optical Microscopy Shared Resource under the direction of Dr. Mariza Miranda, Scientific Director.