Our immune system is our first line of defense against pathogens or disease, including cancer, but sometimes it needs some help. That’s the basis behind an emerging field of treatment called immunotherapy, which involves removing immune cells from a patient, supercharging them and returning them to the body to attack the cancer with renewed vigor.
In the new study, researchers at Cardiff University investigated what biological differences there could be between successful and unsuccessful rounds of treatment in different patients. Over a decade they followed a phase I and II clinical trial examining what’s known as Tumor-Infiltrating Lymphocyte (TIL) therapy, which focuses on the white blood cells that are already at work in the patient’s tumor.
The researchers focused on patients that successfully cleared their cancer after the treatment. They exposed blood samples from patients to tumor cells that had previously been taken from the same patient, and found that the survivors’ killer T cells still showed very strong responses even a year after entering remission.
They used algorithms designed to predict which targets these T cells were recognizing, based on differences between healthy and cancerous cells. And to their surprise, the scientists discovered that the cancer-defeating patients’ T cells were recognizing multiple protein changes in the cancer cells. In contrast, each T cell is usually thought to only target one protein at a time.
“A multipronged killer T cell from a cancer survivor was shown to be substantially better at recognizing cancer than a normal anticancer killer T cell,” said Professor Andy Sewell, lead researcher on the study. “In addition, the ability to simultaneously respond to multiple cancer-associated proteins meant that these T cells could respond to most types of cancer as cancers only needed to express one of the aberrant targets to be identified as dangerous and killed.”
It follows then that the team found large numbers of these multipronged T cells in the blood of patients who successfully cleared their cancer, but none of these cells in patients whose cancer progressed.
The team says that future work will be needed to definitively confirm the link between these T cells and cancer clearance. Understanding what these immune cells are targeting should help improve other cancer therapies as well.
“We have now seen multipronged T-cells in multiple cancer survivors, so examining whether these cells are linked to a good prognosis will be a key next step,” said Dr. Garry Dolton, lead author of the study. “Beyond that, we can genetically engineer this type of T-cell in the laboratory. So, we hope to investigate whether engineered multipronged T-cells can be used to treat a wide range of cancers in a similar way to how engineered CAR-T cells are now used to treat some types of leukemia. That research is still some years away yet, but we are encouraged by our findings so far.”
The research was published in the journal Cell.
Source: Cardiff University
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