Belgian scientists say they are still not sure about the effect of chemotherapy on immunotherapy for mesothelioma. They reached that conclusion after testing several different chemotherapy drugs on mesothelioma cells in the lab.
The combination of chemotherapy and immunotherapy is “chemoimmunotherapy”. It aims to harness the unique powers of each treatment approach. A meta-analysis last May called chemoimmunotherapy the “next frontier” in mesothelioma treatment.
But the new Belgian study on the effect of chemotherapy on immunotherapy highlights how much doctors still do not know about the combo.
Immune Checkpoints Are the Key
When it is working properly, the immune system is supposed to find and kill cancer cells before they become mesothelioma tumors. But mesothelioma cells can hide from the immune system. This makes malignant mesothelioma especially deadly.
Mesothelioma cells hide themselves using immune checkpoints. The proteins PD-1, LAG-3, and TIM-3 are examples of immune checkpoints.
New drugs called immune checkpoint inhibitors block these proteins and unmask mesothelioma cells. Keytruda (pembrolizumab) is one immune checkpoint inhibitor. Opdivo is another one.
These drugs leave mesothelioma cells more vulnerable to immune system attack. They can also make them more susceptible to the effect of chemotherapy on immunotherapy.
Evaluating the Effect of Chemotherapy on Immunotherapy
The primary treatment for mesothelioma is chemotherapy. But it usually only extends mesothelioma survival for a few months.
Doctors know that immunotherapy and chemotherapy drugs affect each other. But they still do not know exactly how. That makes it hard to design the best mesothelioma treatment protocol.
Researchers at the University of Antwerp tested three of the most common mesothelioma chemotherapy drugs. The goal was to measure the effect of chemotherapy on immunotherapy markers like immune checkpoints.
Researchers applied cisplatin, pemetrexed (Alimta), and oxaliplatin to healthy cells and mesothelioma cells. Of the three drugs, cisplatin had the biggest impact on the immunity markers.
“Cisplatin might be a promising treatment to combine with immune checkpoint blocking antibodies since our MPM cell lines were most susceptible to this stand-alone treatment,” writes lead author Elly Marcq.
The other two drugs either downregulated immune checkpoints or did not affect them at all. This was true in both the mesothelioma cells and the healthy cells.
Unfortunately, the team could find “no clear trend” in the effect of chemotherapy on immunotherapy. They conclude that the combination should be studied more extensively.
In the meantime, scientists continue to develop new immunotherapy drugs. The best way for mesothelioma patients to access immunotherapy is to join a clinical trial.
Marcq, E, et al, “Building a Bridge between Chemotherapy and Immunotherapy in Malignant Pleural Mesothelioma: Investigating the Effect of Chemotherapy on Immune Checkpoint Expression”, August 26, 3019, International Journal of Molecular Science, https://www.mdpi.com/1422-0067/20/17/4182
Nowak, AK, “Immune checkpoint inhibition for the treatment of mesothelioma”, May 2, 2019, Expert Opinions in Biological Therapy, Epub ahead of print, https://www.tandfonline.com/doi/abs/10.1080/14712598.2019.1606209?journalCode=iebt20