In a new study, researchers found that injecting tumors with influenza vaccines, including some FDA-approved seasonal flu shots, can turn cold tumors to hot, a discovery that could lead to immunotherapy to treat cancer.
The research was conducted by a team at Rush University.
Changing the microenvironment of tumors to increase the immune system’s response to them has been the goal of countless research and clinical studies.
The majority of patients have tumors that are “cold” — that is, the tumors don’t contain many immune cells, or they have cells that suppress the ability of the immune system to fight them.
Increasing immune cells within a tumor can change it from “cold” to “hot” — more recognizable to the immune system.
Hot tumors show higher rates of response to treatment, and patients with such tumors have improved survival rates.
Currently, some immunotherapies utilize live pathogens (disease-causing organisms) as cancer treatments, but these treatments only have shown lasting effects in a limited number of patients and cancer types.
In the study, the team used a National Cancer Institute database and found that people who had lung cancer and hospitalization for a lung infection from influenza at the same time lived longer than those who had lung cancer with no influenza.
They found a similar outcome in mice with tumors and influenza infection in the lung.
To find an alternative to the limitations of live infection, researchers inactivated the influenza virus, essentially creating a flu vaccine.
They found that direct injection of this vaccine into the skin melanoma of the mice resulted in the tumors either growing slower or shrinking.
The injection made the tumor hot by increasing the proportion of a type of immune-stimulating cells (called dendritic cells) in the tumor, leading to an increase in a type of cells known as CD8+ T cells, which recognize and kill tumor cells.
Importantly, injecting a skin melanoma tumor on one side of the body not only resulted in the reduced growth of that tumor, but also in reduced growth of a second skin tumor on the other side of the same mouse that was not injected.
Based on this result, the team hopes that in patients, injecting one tumor with an influenza vaccine can lead to immune responses in their other tumors as well.
The researchers found that injection of FDA-approved flu shots also resulted in the reduction of tumor growth.
They found that flu vaccines can reduce tumor growth when used alone, whether or not the tumor is responsive to checkpoint inhibitor therapy.
When they combined the flu vaccine with a checkpoint inhibitor together, an even greater reduction in tumor growth occurred.
These results propose that eventually, both patients who respond and those who do not respond to other immunotherapies might benefit from the injection of influenza vaccines into the tumor.
It may increase the small proportion of patients that are now long-term responders to immunotherapies.
Five different influenza shots for the 2017-2018 flu season were used in this research. Four were effective in achieving the same results in fighting tumors.
One flu shot with a synthetic adjuvant (an immune modifier) had no anti-tumor effect and maintained other cells (called regulatory B cells or Bregs) that suppress an immune response.
When the adjuvant was removed from the vaccine, it became effective. Similarly, when the B cells were removed, the vaccine also then became effective.
Clinical trials on average require four phases and can take between eight to 10 years to complete, but because the seasonal influenza vaccine is FDA-approved, the clinical trials for this study might be significantly shorter.
The team says turning one own’s immune system against cancer using something as available and simple as a flu shot may help certain patients with cancer in the near future, instead of within a decade.
One author of the study is Andrew Zloza, MD, Ph.D.
The study is published in PNAS.
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