Written by Chrystal Moulton, Staff Writer. Research shows PD-L1 ligand is a valuable biomarker for predicting survival outcomes in patients with malignant mesotheliomas.
Mesothelioma is a rare aggressive form of cancer commonly associated with exposure to asbestos. (1) The cancer generally arises from the protective layer lining the lungs making it extremely difficult to treat. Median survival from diagnosis among untreated patients is usually less than a year with very little median survival benefit following traditional chemotherapy and radiation.(1) Innovative therapies like immunotherapy, however, has shown very encouraging results even in cases unresponsive to traditional therapies. Results from immunotherapy has prompted researchers to view mesothelioma as a particularly strong immunogenic form of cancer.(2-4) Therefore, finding a biomarker at the tumor site specifically affecting systemic immune response could be a key predictive factor in the treatment of mesothelioma. One possible biomarker is the PD-L1 ligand. The PD-L1 ligand plays a critical role in programmed cell death. When bound to its receptor (PD-L1 binds to the PD-1 receptor), PD-L1 inhibits the formation of activated T-cells causing low T-cell activity. In other words, the body cannot fight the tumor. (5)
In this study, (5) researchers wanted to assess the role of the PD-L1 ligand in predicting survival outcomes in malignant mesothelioma patients.
Between 2000 and 2014, researchers collected information and tissue samples from 119 confirmed cases of malignant pleural mesothelioma. Information on each patient’s medical history, tumor stage and subtype, asbestos exposure, sex, and age was gathered at the beginning of the trial. Tissue samples collected during initial diagnosis were analyzed in the lab for the presence of the PD-L1 ligand within the tumor cells. Patients were then observed prospectively to determine whether there was an association between the presence of PD-L1 on the tumor cells and survival.
In their results, researchers found that the median survival rate over the entire group was 13.8months. However, in individuals who tested positive for the PD-L1 ligand the survival rate was 4.8 months compared to those who were negative for PD-L1 (median survival= 16.3 months) [p=0.012]. No statistically significant associations were found when analyzing the concentration of the PD-L1 ligand expression the tumor cells with median survival (p=0.9). Nevertheless, PD-L1 remained a significant predictor of survival when analyzed together with other significant variables predicting disease outcome (HR 2.08, p=0.021). Furthermore, researchers noted that PD-L1 expression was more prevalent in patients expressing the sarcomatoid and biphasic subtype of mesothelioma versus the epitheliod subtype (p=0.003).
Altogether, researchers found their results to be similar to those of other trials testing the possibility of using PD-L1 as a biomarker in determining clinical outcomes in mesothelioma patients. In this trial, they found that PD-L1 correlated significantly with survival rates and subtype. Therefore, PD-L1 could be used to determine the type of mesothelioma present as well as possible survival times. However, due to small sample size and other factors, researchers stated that more tests will be needed to further evaluate how PD-L1 expression within the cells at the tumor site affects survival rate in mesothelioma patients and whether PD-L1 is useful in predicting the development of a specific subtype of mesothelioma.
Source: Cedrés S, Ponce-Aix S, Zugazagoitia J, Sansano I, Enguita A, Navarro-Mendivil A, et al. (2015) Analysis of Expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Malignant Pleural Mesothelioma (MPM). PLoS ONE 10(3): e0121071. doi:10.1371/journal.pone.0121071
© 2015 Cedrés et al. Creative Commons Attribution License
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Posted August 17, 2015.
Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.
References:
- Hiddinga BI, et al. Mesothelioma treatment: Are we on target? A review. J Adv Res. 2015 May;6(3):319-30.
- Leigh RA, Webster I. Lymphocytic infiltration of pleural mesothelioma and its significance for survival. S Afr Med J. 1982 Jun 26;61(26):1007-9.
- Mansfield AS, et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol. 2014 Jul;9(7):1036-40.
- Yamada N, et al.CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection. Cancer Immunol Immunother. 2010 Oct;59(10):1543-9.
- Cedrés S, et al. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS One. 2015 Mar 16;10(3):e0121071.
