Atezolizumab in non-small cell lung cancer: the era of precision immuno-oncology

CRISPR-Cas, a robust gene-editing technology in the era of modern cancer immunotherapy

“…Immunotherapeutic approaches can be classified into two main categories (1) indirect modification of T-cell’s regulatory elements or immunologically active proteins like interferons, and (2) direct ex vivo manipulation and restoration of T-cells or implanting engineered universal T-cells [ 4 ]. Initial cancer immunotherapy trials have been majorly performed by using some antibodies such as ipilimumab (CTLA-4 targeting antibody), anti-programmed cell death 1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), and anti 4-1BB [ 11 ], alongside with the administration of cancer vaccines like trastuzumab emtansine for advanced her2 + breast cancer [ 12 ], NCS-DNA E7 vaccine against cervical cancer [ 13 ], and atezolizumab for non-small cell lung cancer [ 14 ]. Afterwards, the development of novel combinatorial methods exhibited more reliable and efficient anti-tumor responses in comparison with their separate application [ 15 ].…”

Atezolizumab in advanced non-small cell lung cancer

“…Moreover, the SP142 assay showed the highest inter-pathologist variability, in particular when immune cells were scored (14). These results suggest, at least at this stage, that it is crucial to use the drug's companion/complementary IHC test with validated cutoff for PD-L1 positivity, in order to confidently obtain a clinical benefit specific to that particular treatment (15). Moreover, the IHC technique holds the intrinsic disadvantage of subjective interpretation, in particular when PD-L1 is expressed on both tumor cells as well as on tumorinfiltrating immune cells.…”

“…Therefore, there is also growing interest in developing alternative methods for more reliable PD-L1 quantification. It is certainly possible that observer bias can lead to a shift towards the utilization of nivolumab, which does not require PD-L1 testing, and thus places extra emphasis on reducing inter-pathologist variability (15).…”

Reproducibility of PD-L1 assessment in non-small cell lung cancer—know your limits but never stop trying to exceed them

“…Interestingly, for the 1% cut point sample set there were 4% of irreproducible negative These results are not insignificant for the patients, when compared to the prevalence of a TPS of ≥50% of 30.2% in the screened population in the open-label, phase III KEYNOTE-024 trial, which allowed approval by the FDA of pembrolizumab in the first-line setting in NSCLC patients (6). It is possible that intraobserver bias may lead to a shift towards the choice of the PD-1/PD-L1 inhibitor, whether it requires or not PD-L1 testing, and thus places extra emphasis on reducing inter-pathologist variability (17). In addition, the OPA of interobserver reproducibility was of 84.2% for the 1% cut point sample set, and 81.9% for the 50% cut point sample set.…”