Medical professionals are often left in the dark regarding the unpredictable responses of cancer patients to immunotherapy, a type of treatment that boosts the body's own immune system. This therapy works great for some patients, while ineffective for others. Scientists around the world are grappling with the fundamental questions of why this happens, and how we can make immunotherapy successful for more people.
The fact that the research groups headed by Lonneke van de Poll and Christian Blank at the Netherlands Cancer Institute decided to zoom in on stress did not come out of nowhere. "From a biological standpoint, it's reasonable to assume that stress might affect someone’s response to immunotherapy, given the close interaction between this type of treatment and the body," Van de Poll explains.
Stress can have various effects on the body, including suppressing the immune system, which plays a vital role in immunotherapy. Scientists have observed connections between stress and the immune system in cells as well as animals. For instance, mice subjected to stress appear to respond less well to immunotherapy.
The researchers conducted an analysis of data and biological materials they had collected for the PRADO-study, which examined the effects of immunotherapy prior to surgery in melanoma patients, a type of skin cancer. 28 out of 88 patients reported that they experienced high-stress levels before their treatment. And as it turned out, “these same patients responded less well to the therapy”, Blank concludes. “Their tumors were cleared out less effectively, and the group saw a higher recurrence rate over the following two years compared to patients with lower stress levels: 26 percent, compared to 9 percent.”
"This correlation seamlessly aligns with what many physicians already suspected", explains Van de Poll. "Many medical oncologists with whom we discussed these results weren’t surprised in the slightest. However, we are the first to demonstrate these effects so clearly in patients." Blank: "We don't yet know if stress is the actual cause of the difference in treatment results, but we tried to put everything in place in our analyses to rule out other causes."
Interestingly, a recent international study shows that melanoma patients who use beta blockers for their hearts respond better to immunotherapy – but only if they use beta blockers that can also affect the immune cells. This study may not have been looking into stress, but beta blockers do block the stress receptors, which means that the results hint towards a potential direction in which the researchers of the Netherlands Cancer Institute can take their own search.
“We hope to be able to confirm our findings in a larger study,” Blank says. They intend to do so as part of the international NADINA study that he initiated at the Netherlands Cancer Institute. “We also intend to set up a patient trial to discover whether a decrease in stress can influence immunotherapy results. We’re considering beta blockers right now.”