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Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Radiotherapy and anti-PD-1/PD-L1 combinations in lung cancer: building better translational research platforms
T Kordbacheh1, J Honeychurch2, F Blackhall1
1Targeted Therapy Group, Division of Cancer Sciences, University of Manchester, UK; Cancer Research UK Lung Cancer Centre of Excellence, Manchester Cancer Research Centre, Manchester, M20 4BX, UK; The Christie NHS Foundation Trust, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M20 4BX, UK.
Abstract:
Despite the unheralded success of immune checkpoint blockade in delivering durable responses for some patients with non-small-cell lung cancer (NSCLC), the majority of patients do not respond. PD-L1 tumour expression and pre-existing tumour T-cell infiltration have been correlated with improved clinical outcomes to anti-PD-1/anti-PD-L1. However, patients with tumours that are negative for PD-L1 expression can also respond to treatment. Strategies to combine other treatment modalities like radiotherapy (RT) with immune checkpoint inhibitors are being investigated as means of improving the response rates to PD-1/PD-L1 antibody blockade. RT induces immunogenic changes in cancer cells, can adaptively upregulate tumour cell PD-L1 expression and can improve the efficacy of anti-PD-1/anti-PD-L1 therapy. How we design future clinical trials in NSCLC also depends on practical considerations of delivering these treatment combinations, such as RT dose, fractionation and field volume, as well as scheduling with immune checkpoint blockade. Here, we review reasons for resistance to anti-PD-1/anti-PD-L1 and how RT may be utilised in combination with these drugs to enhance their effect by building better translational research platforms.
Insights
Radiotherapy (RT) combined with immune checkpoint inhibitors may improve non-small-cell lung cancer (NSCLC) treatment response. This strategy aims to overcome resistance to PD-1/PD-L1 blockade, enhancing durable responses in more patients.
Area of Science:
- Oncology
- Immunotherapy
- Radiation Oncology
Background:
- Immune checkpoint blockade, specifically anti-PD-1/anti-PD-L1 therapy, shows success in non-small-cell lung cancer (NSCLC) but benefits only a subset of patients.
- Tumour PD-L1 expression and T-cell infiltration are biomarkers for response, yet some PD-L1-negative tumours also respond, indicating complex resistance mechanisms.
- Combining radiotherapy (RT) with immune checkpoint inhibitors is a promising strategy to improve response rates in NSCLC.
Purpose of the Study:
- To review the mechanisms of resistance to anti-PD-1/anti-PD-L1 therapy in NSCLC.
- To explore how radiotherapy can be utilized in combination with immune checkpoint inhibitors to enhance treatment efficacy.
- To discuss practical considerations for designing future clinical trials investigating these combined treatment modalities.
Main Methods:
- Review of current literature on immune checkpoint blockade resistance in NSCLC.
- Analysis of the immunomodulatory effects of radiotherapy on cancer cells.
- Discussion of translational research platforms for optimizing combination strategies.
Main Results:
- Radiotherapy can induce immunogenic cell death and upregulate PD-L1 expression, potentially sensitizing tumours to anti-PD-1/anti-PD-L1 therapy.
- Combining RT with immune checkpoint inhibitors may overcome resistance and improve durable responses in NSCLC patients.
- Clinical trial design must consider RT parameters (dose, fractionation, field volume) and scheduling with immunotherapy.
Conclusions:
- Radiotherapy holds potential as a synergistic agent when combined with immune checkpoint inhibitors for NSCLC treatment.
- Further translational research is needed to optimize the combination of RT and anti-PD-1/anti-PD-L1 therapy.
- Strategic integration of RT into immunotherapy regimens could enhance clinical outcomes and expand patient benefit in NSCLC.
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