Rationale of combination of anti-PD-1/PD-L1 antibody therapy and radiotherapy for cancer treatment

AbstractSignificant technological advances in radiotherapy have been made in the past few decades. High-precision radiotherapy has recently become popular and is contributing to improvements in the local control of the irradiated target lesions and the reduction of adverse effects. Accordingly, for long-term survival, the importance of systemic cancer control, including at non-irradiated sites, is growing. Toward this challenge, the treatment methods in which anti-PD-1/PD-L1 antibodies that exert systemic effects by restoring anti-tumour immunity are combined with radiotherapy has attracted attention in recent years. Previous studies have reported the activation of anti-tumour immunity by radiotherapy, which simultaneously elevates PD-L1 expression, suggesting a potential for combination therapy. Radiotherapy induces so-called ‘immunogenic cell death’, which involves cell surface translocation of calreticulin and extracellular release of high-mobility group protein box 1 (HMGB-1) and adenosine-5′-triphosphate (ATP). Furthermore, radiotherapy causes immune activation via MHC class I upregulation and cGAS–STING path way. In contrast, induction of immunosuppressive lymphocytes and the release of immunosuppressive cytokines and chemokines by radiotherapy contribute to immunosuppressive reactions. In this article, we review immune responses induced by radiotherapy as well as previous reports to support the rationa le of combination of radiotherapy and anti-PD-1/PD-L1 antib...
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research