Because the programmed death ligand/receptor1 (PD-1/PD-L1) axis plays a major role in the suppression of the immune system, allowing tumors to evade immune detection, blocking these transmembrane proteins has emerged as a promising, new therapy for different types of cancers.
The levels of PD-L1 protein expression in a tumor can predict the response to drugs targeting this pathway. However, until now, the tools to measure PD-L1 were limited, with no standardized immunohistochemical methods and a recurrent inconstancy of antibodies.
With the aim to correlate PD-L1 mRNA expression with clinical variables in primary breast carcinomas, a team of researchers from Yale School of Medicine, New Haven, Connecticut, developed a fluorescent RNAscope paired-primer assay to quantify PD-L1 mRNA levels in 636 stage I-III breast carcinomas on two sets of tissue microarrays.
The researchers verified that PD-L1 mRNA was identified in roughly 60% of all breast tumors analyzed, with higher PD-L1 mRNA expression significantly correlating with increased numbers of tumor infiltrating lymphocytes (TILs), a phenomenon associated with an estrogen receptor-negative status of breast tumors.
Moreover, the data revealed that expression of PD-L1 mRNA was associated with longer recurrence-free survival, a parameter that remained significant in multivariate analysis such as age, tumor size, histologic grade, nodal metastasis, hormone receptor, HER2 status, and the amount of TILs in the tumor microenvironment.
“This is exciting because these findings provide the rationale to test PD-L1 targeted therapies in breast cancer with the hope of further improving cure rates in early stage breast cancer,” said co-author Lajos Pusztai, MD, DPhil, professor of Medical Oncology and chief of Breast Medical Oncology at Smilow Cancer Hospital at Yale Cancer Center in New Haven, Connecticut
The results from this study, published in the journal Cancer Clinical Research, highlight the importance of assessing PD-1/PD-L1-targeted therapies in breast cancer. So far, this type of immunotherapy has already resulted in lasting responses and improved survival in metastatic renal cancer, melanomas, and lung carcinomas.