Overview

The immune system is remarkable. It protects our body from infections and diseases by identifying foreign disease-causing bacteria and viruses. Cancer cells, too, behave the same way by developing a mechanism that allows them to evade the immune system and treatments. And a new study has shown for the first time how these cancer cells resist immunotherapy by “hiding” within one another.

The science and other stuff to know

Immunotherapy drugs, such as immune checkpoint inhibitors (ICI), help your immune system fight cancer. And they’ve demonstrated impressive outcomes. Unfortunately, while these ICI drugs are very effective, only 20 to 30 percent of the patients will respond to the treatments, and most patients will often relapse.

In a recent study published in the journal eLife, researchers from Tel Aviv University have demonstrated how these tumor cells evade immunotherapy. Using mouse models and clinical human samples, the team developed several mouse tumor models that stop responding to immunotherapy after initial treatment.

“Examining cells from these tumors revealed that when the immune system attacks, they reorganize by getting inside one another. This allows some cancer cells to hide under many layers of cell membranes. At this point, killer T-cells can identify and inject the outer cell with toxic granules, but it can’t reach the cells inside,” the researchers noted in the study.

The cancer cells’ ability to hide within one another implies that they can detect when the immune system is attacking. This happens because they can detect toxic granules that killer T-cells release, allowing them to hide.

The team also analyzed tumors with fluorescently labeled cell nuclei and membranes. They found that cell-in-cell cancer formation was more prevalent in immunotherapy-treated tumors, particularly in sites associated with tumor cell death.

So what?

Immunotherapy has become a viable treatment option for cancer patients. Unlike chemotherapy and radiation, it doesn’t target cancer itself. Instead, it enables a patient’s immune system to attack the disease. This finding of how cancer cells escape the immune system could guide future research and help identify novel targets for immunotherapy. It can also set the framework for designing more effective cancer treatments.

“This previously unknown mechanism of tumor resistance highlights a current limitation of immunotherapy,” explained senior author Yaron Carmi, Ph.D., principal investigator at the department of pathology, Sackler School of Medicine, Tel Aviv University, in a press release. “Over the past decade, many clinical studies have used immunotherapy followed by chemotherapy. But our findings suggest that timed inhibition of relevant signaling pathways needs to occur alongside immunotherapy to prevent the tumor from becoming resistant to subsequent treatments.”

What’s next?

This groundbreaking discovery is a step closer to a future of precision oncology where cancer treatments directly contribute to patients’ health and life in the long term. To extend the benefits of immunotherapy, cancer research institutions are working to identify new and more effective ways to improve the immune response to the disease.