Researchers have taken a big step toward better characterizing your mesothelioma. Doing so will help mesothelioma specialist doctors score immediate homeruns with the medicines they choose.
A big problem for them — and you — is that they can’t really be sure if a treatment will be the most effective choice. It might be. Then again, it might not.
The only way to find out is to try it. But that tactic potentially uses up invaluable time in your fight against mesothelioma.
Now, researchers from the University of Chicago have produced findings that could eventually eliminate a lot of the guesswork for your mesothelioma doctor.
The researchers examined mesothelioma tissues that had been already characterized with the aid of super-accurate gene-expression data.
The data allowed the specimens to be divided into subgroups based on the expression of immune-related genes. From these, the researchers were able to identify associated immune escape mechanisms.
Mesothelioma Benefits from Immune Escape
Immune escape refers to the ability of organisms — like cancer cells — to avoid destruction at the hands of the body’s natural immune system.
Immune escape is pronounced in tumors that are inflamed. The researchers noted that mesothelioma tumors are often inflamed.
They also noted that the flavor of the inflammation in mesothelioma cells is distinct from that of other cancers.
“Malignant mesothelioma is commonly associated with an inflammatory reaction, although the specific patterns of immune escape remain incompletely understood,” the researchers stated.
As they pondered further, the researchers determined that inflamed mesothelioma cells have significant immune escape activity. This activity involves multiple immune cell elements.
Consequently, “inflamed and non-inflamed malignant mesothelioma may require differential treatment strategies for immunotherapy,” the researchers then realized.
The researchers said they wanted to conduct this investigation because of the promise shown by immunotherapy in cancers with various biomarkers.
The biomarkers of interest to them included immune signatures, CD8 tumor infiltrating lymphocytes, and expression of the immune checkpoints PD-1 and PD-L1. All of these are indicators of immune escape.
Mesothelioma Clinical Trial Starting
Meanwhile, the University of Chicago has underway a clinical trial that ties into all this. It’s being conducted in two parts.
Part A seeks to determine the antitumor activity in a group of mesothelioma patients, and assess optimal PD-L1 immune-checkpoint cutoff.
The plan is to enroll about 35 mesothelioma patients and treat them with 200 mg of pembrolizumab at 3-week intervals.
At the end of treatment, the researchers will conduct biomarker analysis. They will examine PD-L1 expression and also determine CD8 expression.
The goals are to pinpoint the optimal cutoff for PD-L1 and assess the contribution of CD8 expression. Once this is completed, the clinical trial will move on to Part B.
Part B aims to employ a biomarker enrichment strategy. The biomarker targeted for enrichment is PD-L1.
For Part B, the researchers will enroll an additional 30 mesothelioma patients. Following the PD-L1 enrichment, these patients will receive the same doses of pembrolizumab as did the patients in the Part-A cohort.
At the end of treatment, the researchers will conduct a new assessment and sift through the data. Their findings will be reported at some point in the future.
Whatever they uncover, one thing seems certain. The process of choosing mesothelioma drugs will never be quite the same again.