PD-L1 mRNA Detection in Immunohistochemically Negative Patients: A Complementary Method for a Better Treatment...

Area of Science:

• Oncology
• Immunotherapy
• Molecular Diagnostics

Background:

• PD-L1 inhibitors are approved for cisplatin-ineligible advanced urothelial cancer.
• Therapy requires positive PD-L1 protein expression; negative status limits treatment options.
• Some PD-L1 negative patients respond to PD-L1 therapy, suggesting alternative biomarkers.

Purpose of the Study:

• Investigate the feasibility of PD-L1 mRNA complementary RNA in situ hybridization (RNAish).
• Determine if RNAish can identify PD-L1 responders irrespective of PD-L1 protein status.
• Explore PD-L1 mRNA as a predictive biomarker for immunotherapy in urothelial cancer.

Main Methods:

• Assessed PD-L1 protein and mRNA expression using immunohistochemistry and RNA in situ hybridization.
• Analyzed radical cystectomy tissue from advanced and metastasized urothelial cancer patients.
• Evaluated PD-L1 mRNA expression on tumor cells (TC) and immune cells (IC) and used the Combined Positive Score (CPS).

Main Results:

• PD-L1 protein and mRNA were detected in over 90% of tissues.
• Positive PD-L1 mRNA expression was observed in 77% (TC) and 31% (IC).
• Identified a subpopulation of patients with PD-L1 mRNA-positive but PD-L1 protein-negative status.

Conclusions:

• RNAish is feasible on formalin-fixed tissues for PD-L1 analysis.
• Complementary PD-L1 RNAish identifies a PD-L1 protein-negative, PD-L1 mRNA-positive patient subgroup.
• This subgroup may benefit from PD-L1 therapy, broadening treatment eligibility.