Flu Vaccine May Transform Tumors from “Cold” to “Hot”

Introduction to Immunotherapy

Immunotherapy has emerged as a groundbreaking cancer treatment that leverages the body’s immune system to combat cancer cells. This innovative approach offers an alternative to traditional treatments like chemotherapy and radiation, which often come with numerous side effects. Despite its promise, several challenges persist in effectively implementing immunotherapy in clinical settings.

Understanding “Hot” and “Cold” Tumors

Immunotherapy tends to be most effective for patients with “hot” tumors. These tumors are characterized by a significant presence of immune cells in their surrounding environment, which facilitates the eradication of cancer. Patients with “hot” tumors generally experience better treatment responses and improved survival rates. Conversely, many patients have “cold” tumors, which lack immune cells or contain regulatory immune cells that suppress the immune response.

Transforming Cold Tumors

One potential method to convert a “cold” tumor into a “hot” one involves the introduction of foreign pathogens, such as bacteria or viruses, to the tumor site. This can initiate a robust immune response that encourages the immune system to recognize and attack the tumor.

Research Findings

Researchers at Rush University Medical Center examined data from the Surveillance, Epidemiology, and End Results (SEER) database. They discovered that lung cancer patients hospitalized for the flu had lower cancer mortality rates, leading to the hypothesis that influenza virus exposure could enhance the immune response against tumors. To investigate this, they conducted experiments on mice.

Study Insights

Andrew Zloza, an assistant professor in Rush Medical College’s Department of Internal Medicine and the study’s senior author, noted, “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.” The team found that injecting heat-inactivated influenza virus into tumors resulted in reduced tumor growth and also provided protection against subsequent influenza infections. Their findings were published in the journal *Proceedings of the National Academy of Sciences*.

Effectiveness Against Metastatic Tumors

The researchers demonstrated that the heat-inactivated influenza vaccine may be effective against metastatic tumors as well. In their experiments, they observed a systemic anti-tumor response, where the injection into one tumor site reduced growth in a tumor on the opposite side.

Potential for Repurposing Flu Vaccines

Zloza expressed optimism about repurposing seasonal flu vaccines for cancer treatment, stating, “Since these have been used in millions of people and have already been shown to be safe, we thought using flu shots to treat cancer could be brought to patients quickly.” The commercial flu vaccine was effective in reducing tumor growth, enhancing responses to cancer immunotherapy, and providing protection against influenza infections in a mouse model.

Mechanisms of Anti-Tumor Immunity

The researchers identified a mechanism behind the anti-tumor immunity related to intratumoral vaccination. This vaccination increased levels of dendritic cells, which stimulate the immune system, as well as CD8+ T cells that target and destroy cancer cells.

Future Implications

Based on their research, the team proposed that injecting commercially available flu vaccines into accessible tumors could offer both protection against influenza and improve anti-cancer immune responses. Zloza remarked, “Eventually both patients who respond and who do not respond to other immunotherapies might benefit from the injection of influenza vaccines into the tumor, and it may increase the small proportion of patients that are now long-term responders to immunotherapies.”

Conclusion

The study highlights a novel approach to enhance the effectiveness of immunotherapy for cancer patients, potentially changing the landscape of cancer treatment.

References

Newman, J. H. et al. Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer. *Proc Natl Acad Sci USA* 117, 1119–1128 (2020).
Nancy DiFiore. Can the flu shot help fight cancer? *EurekAlert!* (2020).
Image by Arek Socha from Pixabay.