What question did this study set out to answer?

To determine whether measuring the direct functional engagement of the PD-1/PD-L1 complex improves response prediction to checkpoint immunotherapy compared to measuring PD-L1 expression alone in non–small-cell lung carcinoma.

February 23, 2023Journal of Clinical OncologyOpen Access

Functional Engagement of the PD-1/PD-L1 Complex But Not PD-L1 Expression Is Highly Predictive of Patient Response to Immunotherapy in Non–Small-Cell Lung Cancer

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To determine whether measuring the direct functional engagement of the PD-1/PD-L1 complex improves response prediction to checkpoint immunotherapy compared to measuring PD-L1 expression alone in non–small-cell lung carcinoma.
Assessed functional readouts of PD-1/PD-L1 molecular interaction in combination with PD-L1 expression levels to stratify individuals with non–small-cell lung carcinoma receiving checkpoint immunotherapy.
Functional interaction assessment identified approximately 24% of individuals who had low PD-L1 expression but high PD-1/PD-L1 binding and could benefit from checkpoint immunotherapy.
Combining functional interaction with expression levels prevented the misclassification of individuals with high PD-L1 expression who fail to respond to therapy and remain vulnerable to adverse side effects.

Implication

Biomarker analysis reveals that PD-1/PD-L1 complex engagement predicts immunotherapy response in non–small-cell lung cancer, indicating superior patient selection over PD-L1 expression alone.

Abstract

The functional readout of PD-1/PD-L1 interaction as a predictive biomarker for the stratification of patients with non-small-cell lung carcinoma, combined with PD-L1 expression, should significantly improve the response rates to immunotherapy. This would both capture patients excluded from checkpoint immunotherapy (high PD-1/PD-L1 interaction but low PD-L1 expression, 24% of patients) and additionally avoid treating patients who despite their high PD-L1 expression do not respond and suffer from side effects.

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Cite This Study

Sánchez‐Magraner et al. (2023) studied this question.

synapsesocial.com/papers/69d84d748c03fbaff8beee24 https://doi.org/10.1200/jco.22.01748

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Implication

Biomarker analysis reveals that PD-1/PD-L1 complex engagement predicts immunotherapy response in non–small-cell lung cancer, indicating superior patient selection over PD-L1 expression alone.

Functional Engagement of the PD-1/PD-L1 Complex But Not PD-L1 Expression Is Highly Predictive of Patient Response to Immunotherapy in Non–Small-Cell Lung Cancer

Key Points

Implication

Abstract

Discussion

Cite This Study

Functional Engagement of the PD-1/PD-L1 Complex But Not PD-L1 Expression Is Highly Predictive of Patient Response to Immunotherapy in Non–Small-Cell Lung Cancer

Key Points

Implication

Abstract

Discussion

Cite This Study

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