Health Science Reviews

by Lola Lee

Cancer is one of the leading causes of death worldwide, and although major advances have been made in targeting and understanding specific cancers, these therapies have extremely taxing side effects and serve to maintain the disease rather than eradicate it.  Immunotherapy has become a game-changer in cancer treatment by equipping our own body with a means to fight cancer. Immunotherapeutic approaches aim to activate the immune system to recognize and attack tumours. One major drawback of this approach is that cancer has adapted to evade our immune system by utilizing PD-L1, a protein that can inactivate T-cells, preventing them from attacking and degrading cancer cells. Checkpoint inhibitors are antibodies that block proteins like PD-L1 and prevent cancer cells from inactivating T-cells. These inhibitors have led to some remarkable recoveries in some patients, but not all tumours respond to them – why? Cancer tumours can be referred to as “hot” or “cold” tumours.  Hot tumours contain immune infiltrates, such as T-cells, and therefore the addition of checkpoint inhibitors enables reactivation of the T-cells within the tumour to degrade it. However, most tumours are “cold”, meaning they lack inflammation and immune cell infiltrates, therefore making checkpoint inhibitor treatment ineffective. So, how do we turn a cold tumour hot?

Researchers from Rutgers and Rush University discovered that the answer might be within our annual flu shots. In this study, scientists injected FDA-approved seasonal flu vaccines directly into melanoma and breast cancer tumours in mice to test the in vivo effects. Additionally, the scientists also treated the tumours with PBS as a control, adjuvanted flu vaccines, systemic flu vaccination to mimic a normal flu shot, checkpoint inhibitors like anti-PD-L1 antibodies, and finally a combination of the unadjuvanted seasonal flu shot and the checkpoint inhibitor to test for synergistic effects. The researchers then tested the tumour growth rates, immune cell infiltration with a specific focus on CD8+ T cells, systemic immune response via distant tumour shrinkage, levels of regulatory B cells and cytokine production, and immune activation. Notably, they found that intratumoral injection significantly shrank tumours by kickstarting an immune response within the tumour microenvironment. Specifically, the vaccine recruited immune cells to the site of injection, including an increase in the amount of dendritic cells and CD8+ T cells, which are key immune players in recognizing and killing cancer cells, and essentially turns the tumour “hot”.

It gets even more exciting: not only did the flu vaccine help eliminate the injected tumours, but the vaccine spurred a systemic response in that untreated distant tumours also began to shrink. This meant there was broad immune system activation, not just locally at the injection site. The combination of the flu vaccine with the checkpoint inhibitor enhanced the effectiveness of the previous approach by preventing the cancer cells from evading the infiltrating immune cells. This method not only enhanced tumour regression but enabled tumours that were previously resistant to checkpoint therapy alone to become sensitive to the combination immunotherapy. Interestingly, when the team tested adjuvanted flu vaccines, they found that these versions failed to reduce tumour growth. The likely culprit? The boosted immune response increased B cell concentration within the tumour microenvironment, therefore blocking the activated T-cells from fighting the tumour.

Although this study shows extremely promising results with reproducibility, mechanistic insights, and a controlled study design, it should be noted that the experiments were performed on mice, which is not completely reflective of human responses. Secondly, they only tested the flu vaccination on a limited number of cancer tumour types, and lastly, the study is limited in that only the short-term effects were analysed. What makes this discovery so impactful, however, is its simplicity and accessibility. The seasonal flu shot is already widely available, FDA-approved, and generally safe for use—even in cancer patients. By repurposing it as an intratumoral immunotherapy, researchers may have found a low-cost, low-risk way to help more people benefit from immunotherapy.

So, next time you roll up your sleeve for a flu shot, you might be looking at more than just protection from the flu—you might be glimpsing a new frontier in cancer treatment.