Study details and key findings

During the pandemic, some doctors anecdotally reported that some of their patients with cancer who had severe COVID-19 saw their tumors either shrink or grow more slowly.

"We didn't know if it was real, because these patients were so sick," said Ankit Bharat, chief of thoracic surgery at Northwestern University. "Was it because the immune system was so triggered by COVID-19 that it also started to kill cancer cells? What was it?"

To determine if there was a "benefit" to COVID-19 for these cancer patients, Bharat and his team conducted a study using a combination of human cells and animal models.

The researchers found that RNA from SARS-CoV-2 can activate certain signals in the immune system. These signals cause ordinary white blood cells called monocytes to transform into "inducible nonclassical monocytes" (I-NCMs), which are a unique type of immune cell with anti-cancer properties. I-NCMS can move into blood vessels, as well as surrounding tissue where tumors grow.

What makes these cells so special is their dual capability," Bharat said. "Typically, immune cells called non-classical monocytes patrol blood vessels, looking for threats. But they can't enter the tumor site itself due to the lack of specific receptors. In contrast, the I-NCMs created during severe COVID-19 retain a unique receptor called CCR2, allowing them to travel beyond blood vessels and infiltrate the tumor environment. Once there, they release certain chemicals to recruit body's natural killer cells. These killer cells then swarm the tumor and start attacking the cancer cells directly, helping to shrink the tumor."

By analyzing the receptor on the monocytes that SARS-CoV-2 attaches to, Bharat found a compound that closely mimics how the virus binds to the compound to transform it into cancer-fighting cells. In animal tests, the compound, which is called muramyl dipeptide (MDP), reduced tumors by 60% to 70% in mice with human cancers, such as breast, colon, lung, and melanoma.

"We can use a drug to cause the same effect that the RNA of the COVID-19 virus was doing," Bharat said. "By manipulating that pathway through the drug, we might be able to help patients with many different types of cancers, particularly those with stage 4 cancers."

In addition, Bharat noted that this pathway is separate from the T cell immune treatments that are becoming more common in cancer treatments. Although T cell therapies can be effective, they typically only work for a limited time since cancers can quickly find ways to circumvent T cells and become resistant to them.

In comparison, the virus-induced changes in the monocytes don't depend on T cells, and when Bharat tested the approach in mice genetically bred to lack T cells, there was still a strong effect on their tumors from the monocytes. This suggests that monocytes could help boost the body's response to immunotherapy, as well as its ability to fight cancer.

Commentary

According to Marc Siegal, a clinical professor of medicine at NYU Langone Health, the study has some significance, but it is "not a cancer cure and was only seen in mice."

"It reminds us that viruses cause inflammation and rev up the immune system, which can either increase your risk of certain cancers or, paradoxically, cause certain cancers to shrink by activating immune cells against them," Siegal said.

Separately, Jacob Glanville, CEO of Centivax, a biotechnology company, said he wasn't surprised by the findings. "There's a known history of this phenomenon of 'spontaneous regression' following an infection with a high fever in multiple illnesses, dating back as far as doctors have been identifying cancer," he said.

"The presumed mechanism is that a major inflammation event like an infection can tip the scales toward activating the immune system against cancer," Glanville said. However, "[t]he rate of this happening likely isn't yet high enough to justify it as reliable therapy."

So far, the findings are preliminary, and more research is needed before the approach can be used in clinical settings, Bharat said.

"We are in the early stages, but the potential to transform cancer treatment is there," Bharat said. "Our next steps will involve clinical trials to see if we can safely and effectively use these findings to help cancer patient."

In the future, the team said that they hope to develop therapies that can specifically target monocytes to treat cancers that are difficult to manage, which could lead to new treatment options for patients who have tried all other possibilities. (Park, TIME, 11/15; Rudy, Fox News, 11/19; Wigle, New York Post, 11/18; Northwestern Medicine, 11/18; Liu et al., Journal of Clinical Investigation, 11/15)

Stay ahead of the curve with these ready-to-use slides breaking down the biggest trends impacting the oncology market.  Learn about the state of cancer care today and how to position your organization for future success.