LAUSR

Lu S and colleagues made an exhaustive comparison of several biomarker modalities for predicting response to PD-1/PD-L1 checkpoint blockade (1). The type of test impacts patient’s response to therapy and varies according to the country where it is performed. The FDA recommendation include the use of a specific anti-PD-L1 clone while EMA guidelines recommend the use of IHC validated test but this open the possibility to use different way of assay validation among the different laboratories i.e., companion diagnostic versus not companion diagnostic test. The use of the former has high costs and the adoption of an IHC platform depends on the instrument present in a center, and sometimes is company sponsored. In according to other authors, we found a different PD-L1 immunoreactivity on epithelial cells and macrophages by using different anti-PD-L1 antibody clones (SP142 vs. SP263, Roche Ventana, Tucson, AZ) (Figure 1). The lack of specific guidelines leads to discrepancies in technical and/or clinical validation procedures of PD-L1 testing. The authors underlined that IHC has some limitations due to the lack of reproducibility among the different antibody clones, platforms and cut offs used. No other tests are now included in the clinical practice because of the lack of comparison studies that included patients treated with immune checkpoint inhibitors selected by mIHC/ IF, TMB or GEP. The main limitations of mIHC/IF are due to the unstandardized different selection of type of marker combination (epithelial alone or combination with