Correlation of negative PD-L1 expression with TMB-H and MSI-H rates.

e13162 Background: PD-L1 protein expression, tumor mutation burden (TMB) and microsatellite instability (MSI) are majorbiomarkers for PD-1/PD-L1 blockade therapy for solid tumors. We designed a study to evaluate the relevance of these biomarkers. Methods: From April 2018 to December 2018, 197 patients with lung cancer, colorectal cancer, andgastric cancer wereprospectivelyenrolled.Foreachpatient, afreshfrozentissuesampleor FFPE sample wascollected. Each sample was dividedinto3parts for next-generation sequencing (NGS), PD-L1 protein expression evaluation and MSI evaluation. The sequencing library was captured using a 605-gene panel and sequenced at~5,000×coverage.Mutationsinthe NGS datawereidentified,andTMB was then calculated. The PD-L1 protein expression was analyzedby immunohistochemistry, and the MSI was evaluated using a multiplex PCR comprising 5 loci(NR27, NR21, NR24, BAT25, and BAT26). Results: 18.78% (37/197) were detected with high PD-L1 expression (positive tumor cells ≥50%); 5.08% (10/197) ofpatientswere diagnosed as MSI-H; 4.06% (8/197) of patients had a TMB-H (TMB > 20 mutations/Mb). Among the 37 PD-L1 positive patients, only one patientwith TMB-Hwas detected, and 3patients were MSI-H. In contrast, among the 14 patients with PD-L1 expression less than 1%, 8patients (57.14%) were detected with TMB-H or MSI-H (3 with TMB-H only, 3 with MSI-H only, and 2 with both). In addition, among all the 10patients with MSI-H, 4patients had TMB-H, indicating that MSI-H may be partly associatedwith high TMB. Conclusions: From our preliminary result, PD-L1 protein expression negative patients tend to have higher rates of TMB-H and MSI-H. For patients with negative PD-L1 expression, it issuggested to evaluate its TMB level and MSI status. This study is ongoing, and more data will be collected to verify these findings.