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Updated: Jun 25, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Clinical approach and utilizing liquid biopsies to interrogate suspected acquired resistance to PD-1 blockade
Dilanka Lakshan De Silva1,2,3, Jia Luo1,4,5
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
PD-1 blockade is now routine for nearly all patients with non-small lung cancer. Acquired resistance to PD-1 blockade - defined generally as an initial response followed later by progression [1-3] is a common yet poorly understood concept. A key clinical challenge to insight has been a lack of standard guidance for clinical management of a case of suspected acquired resistance. The infrequency of performing tumor biopsies and the uncertainty of actionability from tissue sampling likely also contribute to limited insight into the biology of acquired resistance [4]. To address this knowledge gap and to highlight the value of tumor and liquid biopsy, we present a representative case of suspected acquired resistance to PD-1 blockade and propose a multi-modal guide for approaching this clinical scenario.
Insights
Acquired resistance to PD-1 blockade in non-small cell lung cancer is common but poorly understood. This study presents a case and a multi-modal guide to aid clinical management and research into resistance mechanisms.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Biology
Background:
- Programmed cell death protein 1 (PD-1) blockade is a standard treatment for non-small cell lung cancer (NSCLC).
- Acquired resistance, characterized by initial response followed by disease progression, is a frequent clinical challenge.
- Limited insight into acquired resistance stems from infrequent tumor biopsies and uncertain actionability of tissue sampling.
Observation:
- A representative case of suspected acquired resistance to PD-1 blockade in NSCLC is presented.
- Challenges in clinical management due to lack of standardized guidance are highlighted.
- The study emphasizes the importance of tumor and liquid biopsies.
Findings:
- The case illustrates the complexities of managing acquired resistance to PD-1 blockade.
- A multi-modal approach is proposed to address suspected acquired resistance.
- Tumor and liquid biopsies are shown to be valuable tools for understanding resistance.
Implications:
- The proposed guide offers a framework for clinical decision-making in suspected acquired resistance.
- Enhanced understanding of resistance mechanisms can lead to improved treatment strategies for NSCLC patients.
- This work underscores the critical role of comprehensive molecular profiling in guiding cancer therapy.
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