Programmed death (PD)-ligand 1 (L1) expression and mismatch repair (MMR) deficiency across tumor types: Candidates for checkpoint inhibitor based immunotherapy.

Abstract

e14622 Background: The identification of biomarkers associated with response to therapeutic agents has changed the paradigm of cancer treatment into the precision medicine by identification of right targets across cancer types. PD-L1 expression and mutational or neoatigen burden (Mismatch repair (MMR) deficiency) have been actively studied as the predictive biomarkers for the response to immune checkpoint inhibitors. Methods: We have conducted the PD-L1 and hMLH1/MSH2 expression (MMR deficiency) as part of a clinical practice for 430 patients with advanced gastrointestinal (GI) cancer, genitourinary (GU) cancer or rare cancers between June 2012 and March 2016. Herein, we evaluated potential candidates who could be targeted to further immune checkpoint inhibitors. Results: In 430 patients, 414 (96.2%) patients were available to evaluate the status of PD-L1 expression by immunohistochemistry (IHC). Irrespective of tumor-types, overall 26.8% (111 of 414) exhibited expression of PD-L1 in tumor tissues. The PD-L1 expression was examined as follows; 33.5% in HCC, 31.0% in CRC, 27.3% in GC, 25.5% in melanoma, 18.8% in BTC, 16.7% in pancreatic cancer, 15.8% in sarcoma and 13.0% in GU cancer. Among the 394 patients available for MLH1/MSH2 expression, only 18 patients (4.5%) had the MMR-deficient tumors with complete loss of MLH1/MSH2 expression. The MMR-deficiency was observed as follows; 7.9% in GC, 6.7% in HCC, 4.0% in CRC, and 2.7% in sarcoma. On 382 patients evaluable for the status of both PD-L1 and MLH1/MSH2 expression, there was no the significant association between the PD-L1 expression and MLH1/MSH2 loss (p = 0.267) Conclusions: These data may provide useful information and background for future research for immune checkpoint inhibitor across tumor-types. As a single selection biomarker for immune checkpoint inhibitor in various tumor-types, neither the PD-L1 expression nor the MMR deficiency is optimal application in clinical trials.