New evidence suggests that mesothelioma patients whose tumors express two particular proteins do not live as long as other mesothelioma patients.
An international team of scientists including mesothelioma researchers at the National Cancer Institute say ALCAM (also called CD166) and PD-L1 (CD274) are both associated with “significantly decreased” survival in pleural mesothelioma.
Understanding ALCAM and PD-L1
ALCAM is a type I transmembrane protein that regulates cellular processes such as the formation of blood cells that feed a tumor (angiogenesis) and immune response.
In cancers like malignant mesothelioma, it is considered a cancer stem cell marker and is associated with cancer invasion, progression, and spread.
PD-L1 is an immune checkpoint inhibitor that is crucial for modulating immune responses in normal cells. However, in mesothelioma cells,, PD-L1 actually helps them escape detection by the immune system. Past studies have found that PD-L1 is overexpressed in up to 40 percent of mesothelioma tumors.
Searching for Survival Markers
In a new study published in Human Pathology, researchers examined 175 sets of pleural mesothelioma cells including 148 samples of the epithelioid subtype (the most common), 15 biphasic, and 12 sarcomatoid.
When mesothelioma cell samples were evaluated immunohistochemically, twenty-five percent of them were found to express ALCAM and thirty-three percent contained PD-L1-positive cells.
“Overall survival was significantly decreased in the cohort of patients with ALCAM or PD-L1-positive tumors,” writes author Shingo Inaguma, MD, a pathologist with the National Cancer Institute and the Aichi Medical University School of Medicine in Japan.
The scientists identified both ALCAM and PD-L1 as independent risk factors for shorter mesothelioma survival.
Dr. Inaguma and his team conclude, “A combination of these two markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma.”
PD-L1 and Immunotherapy
PD-L1 has already been on the radars of mesothelioma researchers. It is key to the effectiveness of certain new immunotherapy drugs, including pembrolizumab (Keytruda), avelumab, and nivolumab.
These three drugs have all made headlines in the past two years for their potential to improve mesothelioma survival by inhibiting PD-L1. Only patients whose tumors express PD-L1 are considered candidates for Keytruda.
Prognostic tests are particularly critical in mesothelioma, for which few viable treatments exist. Because mesothelioma tends to progress quickly, prognostic tests can help doctors and patients select what are likely to be the most promising treatments for them early in the process.
Inaguma, S, et al, “Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma”, August 12, 2017, Human Pathology, Epub ahead of print