Protein May Be Key to Mesothelioma Prognosis

2153419_biomarker2A protein that downregulates the immune system and has been linked to a number of autoimmune disorders may help doctors predict pleural mesothelioma outcomes.

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is responsible for turning the body’s immune system “off” when an immune response is not needed.

In many people with autoimmune disorders such as lupus, Grave’s disease and celiac disease, the gene responsible for CTLA-4 is mutated. The result is that the immune system attacks the body’s own cells.

But patients with mesothelioma often have the opposite problem. Scientists Italy say an overexpression of CTLA-4 may help mesothelioma cells “hide” from the immune system, allowing tumors to grow out of control.

CTLA-4 and Mesothelioma Prognosis

CTLA-4 may play a role in the growth and spread of mesothelioma, but what is its value as a as a way to predict mesothelioma outcomes?

That was the question for mesothelioma researchers in Genoa and La Spezia, Italy. To answer it, they examined the CTLA-4 levels in the tissue, blood serum, and lung fluid of 45 pleural mesothelioma patients

They discovered that more than half of the mesothelioma cells tested expressed CTLA-4 at some level. The levels varied from one type of tissue to the next.

For example, cells taken from the tumors of people with epithelioid mesothelioma had higher levels of CTLA-4 than tumor cells from people with saracomatoid mesothelioma. When the same patients’ blood serum was tested for CTLA-4, the opposite was true. 

But, regardless of which type of cells were tested, there was a clear link between CLTA-4 expression and mesothelioma prognosis.

“A homogeneous favorable prognostic effect was found for CTLA-4 overexpression in tissue, serum and pleural effusion,” reports lead study author Dr. Silvio Roncella. The prognostic effect was strongest in the cells taken from the lung fluid of people with mesothelioma.

The Bottom Line for Mesothelioma Patients

Because of the small size of the study cohort, the jury is still out on the definitive value of CLTA-4 as a mesothelioma prognostic test, but things look favorable. “Our results would indicate a positive correlation of PE (pleural effusion) sCTLA-4 levels and overall survival in malignant pleural mesothelioma patients,” writes Dr. Roncella.

If larger studies reach the same conclusions, then a lung fluid sample from a mesothelioma patient could be used for more than diagnosis; it may also help predict mesothelioma survival.

CTLA-4 was in the the spotlight earlier this year when a drug designed to stimulate the immune systems of mesothelioma patients by disabling CTLA-4 expression failed to show a response.  The drug, called tremelimumab, is still being tested as a possible way to help boost mesothelioma chemotherapy.


Roncella, Silvio, et al, “CTLA-4 in mesothelioma patients: tissue expression, body fluid levels and possible relevance as a prognostic factor”, May 20, 2016, Cancer Immunology, Immunotherapy, Epub ahead of print

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