Canadian scientists say suppressing certain kinds of immune system cells could improve the effectiveness of immuno-radiotherapy for mesothelioma.
Mesothelioma is a fast-growing membrane cancer caused by asbestos. Doctors have not found a single therapy that can beat it. For most patients, a combination of treatments offer the best survival odds.
Immuno-radiotherapy for mesothelioma combines two types of treatments. Immunotherapy drugs activate the immune system while radiation attacks the tumor directly.
Mesothelioma tumors fight back against both kinds of treatments. But researchers testing a combination of the two may have found a way to make it even more powerful.
How Immuno-Radiotherapy for Mesothelioma Works
Malignant mesothelioma is one of the most treatment-resistant cancers. Doctors have to attack it from many different angles. Immunotherapy and radiotherapy are two of the cancer-fighting tools in their tool chest.
Immunotherapy drugs harness the power of the patient’s own immune system to fight cancer. But the immune system is complex. Immune cells called Tregs try to keep the system in balance. They suppress overactivation of other immune system cells.
Immuno-radiotherapy for mesothelioma brings radiation into the mix to help. Radiation disrupts the DNA inside mesothelioma cells. This makes it harder for tumors to grow and spread. But radiotherapy also triggers the release of Tregs.
The researchers hoped to improve immuno-radiotherapy for mesothelioma by targeting Tregs.
A New Approach to Mesothelioma Treatment
Another advantage to radiotherapy is that it can sometimes produce an abscopal effect. The abscopal effect is when doctors irradiate one tumor but other non-treated tumors also respond. The Canadian team wanted to develop immuno-radiotherapy for mesothelioma that would also capitalize on this effect.
For their experiment, the team used special mice whose Tregs could be easily manipulated. The mice were infected with mesothelioma and underwent radiotherapy. Then they received a drug to disable their Tregs.
“We observed that transient Foxp3+ Treg depletion immediately after…irradiation provided synergistic local control and biased the T cell repertoire toward central and effector memory T cells, resulting in long-term cure,” reports lead author Mikihiro Kohno of the University of Toronto.
This approach to immuno-radiotherapy for mesothelioma also triggered the abscopal effect. It took a few rounds of radiation for this to kick in. The study could make Treg-depeting treatments a regular addition to immunotherapy and radiotherapy for mesothelioma.
Dr. Kohno concludes, “Targeting Tregs immediately after a short course of irradiation could have a major impact on the local response to irradiation and its abscopal effect.”
Immuno-radiotherapy for mesothelioma is still in development. Most patients have chemotherapy and/or surgery before they try other treatments.
Kohno, M, et a, “Foxp3 + Regulatory T Cell Depletion after Nonablative Oligofractionated Irradiation Boosts the Abscopal Effects in Murine Malignant Mesothelioma”, September 18, 2020, Online ahead of print, https://www.jimmunol.org/content/early/2020/09/17/jimmunol.2000487