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Oncotarget. 2017 Aug 24;8(44):77415-77423. doi: 10.18632/oncotarget.20492. eCollection 2017 Sep 29.

Correlating programmed death ligand 1 (PD-L1) expression, mismatch repair deficiency, and outcomes across tumor types: implications for immunotherapy.

Author information

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
The Angeles Clinic and Research Institute, Los Angeles, CA, USA.
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Contributed equally


The identification of biomarkers associated with response to therapeutic agents is central to optimizing patient outcomes. Expression of the immune checkpoint proteins PD-1/L1, and DNA mismatch repair deficiency (dMMR) status may be predictive response biomarkers for immunotherapies, but their overlap requires further study. We prospectively conducted PD-L1 and MMR immunohistochemistry (IHC) on 430 consecutive patients with advanced gastrointestinal (GI) cancers, genitourinary (GU) cancers or rare cancers between June 2012 and March 2016. Overall 393/430 (91.4%) patients were evaluable for PD-L1 expression by IHC. The frequency of tumor PD-L1 positivity (PD-L1+) was 16.5% (65/393). Among anatomic tumor sites PD-L1+ was 28.6% in melanoma, 22.2% in GC, 20.9% in CRC, 12.5% in BTC, 7.1% in GU cancer, 6.7% in HCC, 0% in pancreatic cancer and 0% in sarcoma. Among the 394 evaluable for MLH1/MSH2 expression cases, 18 patients (4.5%) had dMMR tumors. The dMMR was most common in GC (7.1%) followed by 6.7% in HCC, 4.4% in CRC, and 2.7% in sarcoma. Of the 365 patients evaluable for both PD-L1 and MLH1/MSH2 expression, there was a significant association between the PD-L1 expression and MLH1/MSH2 loss (P = 0.01), but not with overall survival within tumor types. PD-L1 status and dMMR are overlapping putative response biomarkers in immunoncology. Clinical trials with biomarker enrichment restricted to PD-L1+ or dMMR may be inadequate to capture the subset of patients who may benefit from immune mediated therapies. More robust immunotherapy biomarkers and careful clinical trial design are warranted.


biomarker; gastrointestinal cancer; immunotherapy; mismatch repair deficiency (dMMR); programmed death-ligand 1 (PD-L1)

Conflict of interest statement

CONFLICTS OF INTEREST The authors have declared that no competing interests exist.

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