The current cancer research strongly focuses on the immune therapies, where the programmed death-1 receptor (PD-1), with its ligands PD-L1 and PD-L2 play an important role. It is known that PD-L1 is frequently up-regulated in a number of different cancers and the relevance of this pathway has been extensively studied and therapeutic approaches targeting PD-1 and PD-L1 have been developed. However, PD-L2 has not received as much attention and its role in modulating tumor immunity is less clear. To identify potential patients who may benefit from PD-1/PD-L1/PD-L2 targeted immunotherapeutics, we used a non-invasive, real-time biopsy for determining PD-L1 and PD-L2 expression in CETCs of breast cancer patients.
CETCs were determined from blood of 66 patients suffering from breast cancer. The number of vital CETCs and the expression of PD-L1 and PD-L2 were investigated using the maintrac method.
PD-L1 expressing CETCs were detected in 95 % of breast cancer patients whereas only 75% patients had PD-L2 positive CETCs. There was no association between the frequency of PD-L1 positive CETCs and progression of cancer disease. We found that the fraction of PD-L1 positive CETCs is significantly higher than the fraction of PD-L2 positive CETCs (63.3% vs. 32.9%; p). Moreover, we observed a significant heterogeneity in PD-L1 and PD-L2 immunostaining intensity across CETCs from the same patients.
Breast cancer patients have detectable CETCs with high frequency of PD-L-1 regardless of stage of disease. PD-L1 seems to be a major factor in immune evasion and may be a promising target of anticancer therapies. Monitoring the frequency of PD-L1 positive CETCs could reflect individual patient’s response for an anti-PD-1/PD-L1 therapy.