Can Influenza Vaccines Trigger Immune Response in Patients With Melanoma?
Posted: Friday, February 14, 2020
Antipathogen vaccines such as the annual influenza vaccine may be useful not only for infection prevention, but also as a way to change tumor cell microenvironments to increase the immune system’s response. Andrew Zloza, MD, PhD, of Rush Medical College in Chicago, and colleagues proposed that repurposing the “flu shot” may improve response rates to immunotherapy and be “quickly translated for clinical care.” Their study findings were published in the Proceedings of the National Academy of Sciences of the United States of America.
“We wanted to understand how our strong immune responses against pathogens like influenza and their components could improve our much weaker immune response against some tumors,” said Dr. Zloza in a Rush University press release.
Researchers created inactivated versions of the influenza vaccine via heat inactivation and chemical lysis. This inactive vaccine was then injected directly into melanoma tumors in mice. This injection reduced tumor growth and prolonged host survival. There was increased antigen presentation by dendritic cells within the tumor as well as an increased number of CD8-positive T cells within the tumor, indicating conversion of “cold” tumors to “hot” tumors.
A bilateral flank experiment was conducted to assess systemic immunity from injection of the inactivated vaccine. After injection of the vaccine into a tumor on one side of the body, both the tumor that was inoculated and untreated tumors on the other side of the body exhibited reduced melanoma growth. Intratumoral injection was found to decrease melanoma growth in hosts previously infected with influenza virus, which suggests that intratumoral inactivated influenza vaccines may be used in hosts who have already cleared that pathogen.
Researchers then combined their vaccine with a PD-L1 checkpoint blockade in the melanoma mouse model and saw further reduced tumor growth. Patients who respond even partially to a checkpoint blockade may therefore benefit from administration of an inactivated influenza virus.
Disclosure: For full disclosures of the study authors, visit pnas.org.