Helping the Immune System Remember How to Fight Cancer Long Term

Cancer immunotherapy, a group of treatments that use the body’s own immune system to help fight cancer, is currently one of the most active areas of cancer research. There are different kinds of immunotherapies, but the overarching goal of these treatments is to trigger the immune system to attack cancer cells – the same way it works when a person has the flu or a cold.

Scientists have spent decades trying to figure out how to get the immune system to recognize and kill cancer cells, but have only more recently discovered methods for doing it. Cancer cells are constantly changing and evolving over time, enabling them to hide from or block the immune system or trick it into leaving them alone. Cancer immunotherapy drugs help the immune system overcome the negative effects of the tumor.

Several clinical trials of cancer immunotherapies are reporting success, shrinking tumors and helping to prolong survival. But these drugs are on the newer side and scientists are still investigating if their effects are permanent or if the tumors change in ways that diminish their effectiveness over time.

To keep cancer away for the long term, the immune system has to remember how to recognize and attack the cancer so if it comes back in the future, the immune cells will be ready to fight and win. The body needs to create “immunological memory” says Surojit Sarkar, Ph.D., a researcher at Pennsylvania State University – and he and his colleagues have now discovered possible ways to help the immune system do just that.

close up portrait of Surojit Sarkar, PhD, Pennsylvania State University

Surojit Sarkar, Ph.D., a researcher at Pennsylvania State University, is studying immunological memory.

“With cancer immunotherapy, what we are doing is pulling off the brakes on the immune system, spurring it to attack the cancer by sending out lots of what are called killer T-cells into the body,” says Sarkar. He likens these killer T-cells to soldiers in a war – in active battle the body sends them out in large numbers to fight off the enemy, in this case, cancer. “Helping to proliferate T-cells is great; it means more soldier T-cells that will kill more cancer cells. But in the long run, if we don’t put the brakes back on – or draw down the soldiers to give them a rest – you will get great clearance of cancer today, but recurrence of cancer may occur in the future,” says Sarkar.

“If we don’t find a way to get the killer T-cells to sustain into memory in the long run, what will happen is the cancer will come back again and there will be no fit soldiers left to fight.” And not only does the immune system need to tell the killer T-cells to stop fighting once the cancer is gone, but it also needs to keep a certain number of soldiers at the ready in case the cancer comes back in the future, says Sarkar.

Building the Immune System’s Version of the Army Reserves

Just like the U.S. Army keeps a force of trained reserves, the immune system needs a team of immune cells that have the knowledge, skills, and tools at the ready in case of a future attack. The human body’s equivalent to the Army Reserve is immune memory cells.

After the immune system is done fighting an infection, it reduces the number of killer T-cells out in force and transitions the killer T-cells that are left to immune memory cells. Sarkar explains that memory cells have experienced the enemy the first time, so they remember it and the next time the enemy appears, they can react more quickly.

When it comes to cancer immunotherapies, the issue, according to Sarkar, is that these treatments need a way to help the body create immune memory cells once the immune system is done fighting the cancer.

One potential strategy has to do with vitamin D. Sarkar has discovered that vitamin D may act like immunological brakes – promoting the formation of a broad, functional immune memory pool. Now, with the help of a multi-year $792,000 grant from the American Cancer Society, Sarkar and his team are going to research the specific role of vitamin D in creating immune memory. Their grant kicks off in July.

His goal is to figure out the vitamin D needs of patients and how soon after an immunotherapy treatment the doctor would need to give it to them to be most effective at generating a long-lived protective immune memory pool. “We want to determine if vitamin D should be given at the time of vaccination or immunotherapy or does the patient need to maintain good levels of vitamin D throughout treatment,” says Sarkar.

Vitamin D Could Be Part of Multi-Pronged Approach to Building Immune Memory

The other potential strategy Sarkar has discovered that may help transition killer T-cells to immune memory cells has to do with regulatory T-cells. Sarkar and his Pennsylvania State University colleague, Vandana Kalia, Ph.D., have been studying the function of regulatory T-cells and published their findings online June 16 in the journal Immunity.

“We found that regulatory T-cells help in the creation of memory cells, so if we can enhance the memory-accelerating function of regulatory T-cells, this may help transition the active killer T-cells into immune memory cells more efficiently,” says Kalia.

close up portrait of Vandana Kalia, PhD, Pennsylvania State University

Sarkar and his Pennsylvania State University colleague, Vandana Kalia, Ph.D., have been researching regulatory T-cells.

“The killer T-cells are like soldiers with their weapons drawn; memory cells have their weapons in a holster, but not drawn. So regulatory T-cells help in the transition from the weapon drawn stage to the weapon in the holster stage,” says Sarkar. “Without the regulatory T-cells, the killer cells crash and burn, and hence don’t become memory cells.”

Sarkar thinks that vitamin D and regulatory T-cell strategies for enhancing immune memory could possibly be combined. “We want to see if we can combine vitamin D and regulatory T-cells to slow down the immune system at the right time,” says Sarkar. “Vitamin D is easy to use because we can administer it from outside in a pill or fluid format. We can essentially put the brakes on the immune system on demand.”

Sarkar plans to spend the next couple of years building the foundational evidence needed to better understand the role of vitamin D in generation and maintenance of immune memory and then will study how effective vitamin D is in enhancing immunotherapeutic approaches to tumors in mice.

“If you have long-lived memory cells, you will have better remission. If you think about a child’s life, we don’t want them to live in constant fear of when the cancer may come back,” says Sarkar. His hope is that his research into creating immune memory for fighting cancer can change that. “We hope that this research will help immunotherapies not only secure the present, but also ensure the cancer is gone forever, or at least if not gone, your body will already have soldiers stationed to take care of the cancer for the rest of your life.

American Cancer Society news stories are copyrighted material and are not intended to be used as press releases. For reprint requests, please see our Content Usage Policy.