Abstract
Radiotherapy is an effective local treatment modality of NSCLC. Its capabilities of eliminating tumor cells by inducing double strand DNA (dsDNA) damage and modulating anti-tumor immune response in irradiated and nonirradiated sites have been elucidated. The novel ICIs therapy has brought hope to patients resistant to traditional treatment methods, including radiotherapy. The integration of radiotherapy with immunotherapy has shown improved efficacy to control tumor progression and prolong survival in NSCLC. In this context, biomarkers that help choose the most effective treatment modality for individuals and avoid unnecessary toxicities caused by ineffective treatment are urgently needed. This article summarized the effects of radiation in the tumor immune microenvironment and the mechanisms involved. Outcomes of multiple clinical trials investigating immuno-radiotherapy were also discussed here. Furthermore, we outlined the emerging biomarkers for the efficacy of PD-1/PD-L1 blockades and radiation therapy and discussed their predictive value in NSCLC.
Highlights
Non-small cell lung cancer (NSCLC) is a prevalent disease with high morbidity and mortality, accounting for 85% of lung cancer cases
Delivery of radiotherapy and PD-1/PD-L1 blockades in the clinical practice is still imprecise, with a limited ability to identify patients who will get survival benefit from immune blockades and radiation treatments or patients who are likely to suffer from adverse effects caused by these modalities
4.3.1 Tumor Inflammation Signatures Recently, multiple studies found that gene expression analysis related to tumor microenvironment through RNA isolated from formalin-fixed paraffin-embedded (FFPE) samples from patients before treatment with PD-1/PD-L1 blockades was predictive of treatment outcome in various cancer types [74, 75, 122, 123]
Summary
Non-small cell lung cancer (NSCLC) is a prevalent disease with high morbidity and mortality, accounting for 85% of lung cancer cases. A range of immune-related toxicities such as colitis, hypophysitis, pneumonitis, thyroiditis, inflammatory arthritis, and more have been reported [9] Under these conditions, it has been recognized that combining anti-PD-1/ PD-L1 treatment and radiation therapy could help overcome treatment resistance and improve survival benefits of patients synergistically. Delivery of radiotherapy and PD-1/PD-L1 blockades in the clinical practice is still imprecise, with a limited ability to identify patients who will get survival benefit from immune blockades and radiation treatments or patients who are likely to suffer from adverse effects caused by these modalities For this reason, predictive biomarkers are in urgent need in order to tailor the treatment strategy for individuals. We will outline the emerging biomarkers which show potential to predict response to PD-1/ PD-L1 inhibitors as well as radiotherapy in NSCLC
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