Objective:

To identify PD-1/PD-L1 and CTLA-4/CD80 interaction states as enhanced predictive biomarkers for patient stratification to anti-PD-1/PD-L1 therapies in NSCLC.

Approach:

• Study Design: Utilized the QF-Pro® platform to quantify CTLA-4/CD80 and PD-1/PD-L1 interaction states in FFPE samples from 67 NSCLC patients treated with anti-PD-1/PD-L1 therapies.
• Analysis Method: Measured FRET efficiency to assess interaction states and correlate with overall survival (OS) and progression-free survival (PFS).

Key Findings:

• High PD-1/PD-L1 interaction predicts improved response rates via overall survival (OS) and progression-free survival (PFS).
• High CTLA-4/CD80 interaction (FRET efficiency ≥6.41%) correlates with improved OS and PFS in response to anti-PD-1/PD-L1 therapies.
• Patients with concurrently high PD-1/PD-L1 and CTLA-4/CD80 interactions exhibited the highest response rates, suggesting a synergistic interplay.
• Neither biomarker predicted response to chemotherapy in a separate cohort of lung adenocarcinoma patients, confirming specificity for ICI therapy.

Interpretation:

The study highlights the clinical relevance of CTLA-4/CD80 interaction as a predictive biomarker for anti-PD-1/PD-L1 therapies in NSCLC.

Limitations:

• The study is limited to a specific cohort of NSCLC patients.
• Findings may not be generalizable to other cancer types or treatment modalities.

Conclusion:

These results highlight the potential of QF-Pro® as a robust tool for stratifying NSCLC patients for ICI treatment.