Enhancing the efficacy of immunotherapy using radiotherapy.
Synat KeamSuki GillMartin Andrew EbertAnna K NowakAlistair M CookPublished in: Clinical & translational immunology (2020)
Recent clinical breakthroughs in cancer immunotherapy, especially with immune checkpoint blockade, offer great hope for cancer sufferers - and have greatly changed the landscape of cancer treatment. However, whilst many patients achieve clinical responses, others experience minimal benefit or do not respond to immune checkpoint blockade at all. Researchers are therefore exploring multimodal approaches by combining immune checkpoint blockade with conventional cancer therapies to enhance the efficacy of treatment. A growing body of evidence from both preclinical studies and clinical observations indicates that radiotherapy could be a powerful driver to augment the efficacy of immune checkpoint blockade, because of its ability to activate the antitumor immune response and potentially overcome resistance. In this review, we describe how radiotherapy induces DNA damage and apoptosis, generates immunogenic cell death and alters the characteristics of key immune cells in the tumor microenvironment. We also discuss recent preclinical work and clinical trials combining radiotherapy and immune checkpoint blockade in thoracic and other cancers. Finally, we discuss the scheduling of immune checkpoint blockade and radiotherapy, biomarkers predicting responses to combination therapy, and how these novel data may be translated into the clinic.
Keyphrases
- early stage
- combination therapy
- locally advanced
- cell death
- radiation induced
- radiation therapy
- dna damage
- immune response
- clinical trial
- oxidative stress
- papillary thyroid
- end stage renal disease
- ejection fraction
- newly diagnosed
- rectal cancer
- squamous cell
- chronic kidney disease
- randomized controlled trial
- endoplasmic reticulum stress
- stem cells
- spinal cord
- prognostic factors
- spinal cord injury
- cell therapy
- dna repair
- toll like receptor
- pain management
- peritoneal dialysis
- lymph node metastasis
- young adults
- cell proliferation
- replacement therapy
- double blind