Removing Cancer’s Cloak of Invisibility

Copyright Promega.

Copyright Promega.

For decades scientists have been trying to harness the power of our immune system to fight cancer cells. It is not impossible to imagine that our immune system, which is sophisticated enough to fight against a multitude of invaders that threaten our health, should be able to tackle a deadly disease such as cancer. This formed the basis of testing a new type of cancer treatment known as immunotherapy. Immunotherapy for cancer means developing treatments to harness your immune system and using your own immune system to fight the cancerous cells.

But in reality it was hard to make this work. Because, as scientists discovered recently, cancer outsmarts the immune system by wearing a kind of “invisibility cloak”. Cancer is able to fool the immune system from recognizing that it is the enemy and in effect keeps the immune system from destroying it.

In a breakthrough discovery scientists have found a way around this treachery.

The breakthrough is in therapies called ‘checkpoint inhibitors’. Checkpoint inhibitors block the mechanisms that allow some tumor cells to evade the immune system. The drugs ensure that cancer cells are no longer be shielded from the immune system defenses, but are instead recognized as “foreign”.

And these drugs look promising for at least some patients — chipping away at some tough tumors, such as some melanomas, the deadliest kind of skin cancer. They also seem to be working quite well for other types of cancers, including kidney cancer, bladder cancer, head and neck cancers, lymphoma and even perhaps breast and lung cancers.

How does cancer immunotherapy work?

In a normal immune response, the immune system abates invasion by foreign cells by unleashing powerful T-cells to destroy the threat. The T-cells do not attack healthy cells because of signals called “checkpoints” that keep the T-cells from destroying cells that are not a threat. Certain types of cancer trick the system by sending out a checkpoint signal called “PD-1/PD-L1” which deactivates the attacking T-cells. New drugs called “checkpoint inhibitors” block the PD-1/PD-L1 signaling, allowing the T-cells to recognize that the tumors are aberrant cells that need to be destroyed.

A serious concern with checkpoint inhibitors is the potential to damage healthy cells causing serious side-effects which can become life threatening. But results from clinical trials suggest that such occurrences are relatively rare.

A second cause for concern is the longevity of the checkpoint inhibitors. One of the drawbacks of traditional chemotherapy is that its effectiveness is not uniform over the length of treatment and is influenced by the patient’s genetic makeup, the type of cancer and the stage at which it was diagnosed. Although checkpoint inhibitors seem to keep going a lot longer, even in patients who are recalcitrant to standard chemotherapy, the jury is still out.

But the bigger elephant in the room is the cost of treatment: the high price tag might prove to be a deterrent; but the hope is to figure out a way to cut the costs such that patients may not have to stay on the drugs indefinitely. That is possible because when patients stop treatment, the immune system, over time, creates memory which instructs the body to keep it cancer- free. The T-cells remember how to attack the tumor and stop the cancer from putting up a shield. So those T-cells continually keep that cancer under control even in the absence of further treatment.

Although the field is too young to really know just how well these checkpoint inhibitors work, and for how long, many scientists are in agreement that it will take a combination of checkpoint inhibitors to get the most out of our immune systems to fight cancer. It is the age of personalized medicine and scientists are now setting out to answer who needs a single checkpoint inhibitor and who might need a combination of several to tap the full potential of this therapy.

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Radhika Ganeshan

Technical Services Scientist at Promega Corporation

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