How to Fight Cancer: A Flu Shot Story

Physicians and scientists at Rush University Medical Center observed a fascinating phenomenon. It has the potential to change the way cancer is treated. A boost to current cancer treatments like immunotherapy that could increase patient survival and augment time spent with loved ones.

The comfort of patients is taken very seriously by health professionals. Besides being physically present and supportive during chemotherapy, an even better solace would be provided by these healthcare providers if the unbearable side effects of cancer treatment were diminished altogether.

Conventional cancer chemotherapies are not solely targeted to the cancer. They are non-selective. This means that besides killing cells with high proliferation rates, chemotherapies will poison ”off-target” cell types as well. Hair loss, vomiting, diarrhea, destroyed nails, and heart issues are all among the harsh consequences. The use of such detrimental treatments is only justified because their benefits ; eradicating cancer outweighs the risks of dying from it. This comes at the personal cost of awful days, weeks, even months of suffering from side effects associated with therapy.

To give a better quality of life to those diagnosed with cancer, scientists are working restlessly to develop new treatments targeted directly to the tumor.

Cancer and Flu Virus: Friends with Patient Benefits

In an effort to understand the reasons why some cancer patients have a better survival rate than others, researchers compiled data from medical records and found out that patients diagnosed with lung cancer who have been infected by the flu virus had a better survival rate compared to non-infected patients. These findings raised a lot of interest from the scientific community. How would that be? Does Influenza — the flu virus — directly infect cancer cells? Could the regression of the tumor be linked to an indirect effect of the viral infection? Does the viral infection trigger an immune response as it usually does but this time leading to a cellular cooperation that will end up destroying the cancer cells? Well, evidence points toward this last hypothesis. To address it, scientists reproduced the scenario in a mouse model.

The Hotter The Better

One of the “dernier cri” of cancer treatment that unites many researchers in the world of oncology is immunotherapy. It is a type of therapy that plays on the endogenous immune response to better target cancer. However, in order for immunotherapy to be effective, immune cells have to be present inside tumor at the time of the treatment. Scientific literature confirms that tumors containing a lot of “active” immune cells are more responsive to imunotherapies. These are, in fact, qualified as “hot” tumors, as opposed to “cold” ones which have low numbers of — sometimes inactive — immune cells. One would conclude from the predictive nature of these “immuno-phenotypes” that cancer patients with hot tumors are more likely to live longer after treatment.

How do we turn a “cold” into a “hot” one? That is the million-dollar question. This question is also relevant to social media platforms like Instagram, but that is a different topic ;)

The Flu Virus Affects Tumor Growth

In the study reported by Proceedings of the National Academy of Sciences journal (PNAS), the group of scientists from Rush University Medical Center mimicked what could happen in humans by injecting inactivated flu virus into patient-derived melanomas that were implanted in mice. The results were so impressive that they could potentially address the million-dollar question.

They found that the presence of Influenza virus in tumors correlated with an increased number of intratumoral dendritic cells. These cells, also called antigen-presenting cells (APCs), are known to recruit CD8+ (cytotoxic) T cells for the purpose of killing cancer cells. As a result of this effective recruitment, tumors in mice exposed to Influenza virus shrank. These fascinating results were also observed in a triple negative breast cancer model (TNBC).

Influenza virus infection managed to “heat” certain types of solid tumors that often do not respond durably to standard cancer therapies. The researchers hypothesized that tumors could now demonstrate a better response to treatments such as checkpoint blockade — a specific class of immunotherapy.

Cancer Immunotherapy — Checkpoint Inhibitors

Tumors have several ways to keep growing despite permanent controls and regulations orchestrated by the immune system. Those who are familiar with my writings can by now tell that I’m obsessed with spy movies. They are not totally wrong. To be honest a flagrant resemblance facilitates the analogy. In spy movies, the bad guys are always trying to escape the authorities. They navigate incognito, under the radar, hiding their faces from surveillance cameras. This being said, it could also work the other way around — with the good guys trying to escape the bad guys. In any case, the concept would be similar. By faking their identities, cancer cells, aka “the bad guys”, acquire the capability to escape the surveillance of cells comprising the immune system, aka the “good guys”. Tumor cells manage to make the immune system “believe” they are part of the same team, team “self”.

The immune system has a precise way of differentiating cells as “Self” versus “non-Self” — the latter being cancer cells in our case.

It can be described as 2-step security process.

• Step one: the recognition of the designated cells based on the signature molecules (i.e. antigen) dendritic cells present to T-cells.

• Step two: the destruction the culprit-designated cells. Unless the designated cell proves its identity as a member of the “self”,the death sentence will be applied.

Checkpoints: Proof of Identity

Cells have to prove their identity via checkpoints. These checkpoints are expressed on the surface of immune cells waiting to be activated by ligands that are usual expressed only on cells from the “Self”. The activation of checkpoints triggers an inhibitory signaling pathway telling the immune cell to abort the mission. In some cancers, cells exploit checkpoint ligands to outsmart the immune system and evade immune response.

With this in mind one can now understand the mechanism of action behind checkpoint blockade immunotherapy.

Checkpoints Inhibitors

Scientists used a blockade strategy to prevent cancer cell evasion. Such immunotherapy prevents checkpoint activation and allows effector T-cells to attack and eliminate cancer cells. Two of the famous check points inhibitors are named Keytruda and Opdivo. They both are monoclonal antibodies targeted to PD-1, a checkpoint molecule expressed on T cells. Its ligand, PD-L1, is enriched in many cancers including melanoma.

Combination therapy

Checkpoints inhibitors show encouraging results but their success is tightly linked to the presence of immune cells in the tumor. The combination of flu vaccine and checkpoint inhibitor was thus investigated. Flu vaccine reduced tumor size when used alone. This response was independent from response of tumors to checkpoint inhibition. However, the combination induced an even greater regression of the tumors, indicating a synergetic effect between flu vaccine and checkpoint inhibitors.

These experimental results are really promising for the development of future cancer treatments. Indeed, these findings need to be verified in the human context. The only way to generate that context would be to launch clinical trials. This process takes time. Time that cancer patients can’t afford. In this specific case, time can be reduced. Flu vaccines and checkpoints inhibitors are well known treatments and have already been FDA-approved individually. This fortunate circumstance will allow this combination to shift into a designated fast track for FDA-approval. If this combination therapy shows irreproachable positive results in clinical trials, cancer patients will benefit from it even sooner.

Even greater than the fantastic results obtained by the team from Rush University Medical Center, this study brought to the front the importance of interdisciplinary opening the can of endless possibilities. Also the fact flu vaccine contribute to fight cancer brings an additional motivation to get vaccinated.