Radiotherapy enhances responses of lung cancer to CTLA-4 blockade.
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Date
2019-03-06Author
Wilkins, A
McDonald, F
Harrington, K
Melcher, A
Type
Journal Article
Metadata
Show full item recordAbstract
Formenti et al. have recently reported the clinical outcomes and translational readouts of a trial of the anti-CTLA-4 inhibitor, ipilimumab, in combination with palliative radiotherapy in 39 patients with non-small cell lung cancer. A radiological response was seen in 18% of patients and 31% of patients experienced disease control. These clinical outcomes appear to be superior to historical studies using ipilimumab alone and suggest that radiation may have triggered systemic, so-called abscopal, immune responses in some patients. Induction of interferon-beta (IFN-β) and maximal expansion and contraction of distinct T cell receptor clones were the most significant factors predicting response. Importantly, established predictive biomarkers of response to immunotherapy alone, including the expression of PD-L1 in diagnostic biopsies and tumour mutational burden, did not predict response. The report provides important human qualification of pre-clinical mechanistic insights indicating that abscopal responses can be generated with optimised radiotherapy fractionation schedules and anti-CTLA-4 inhibition. Additionally, an intriguing mechanism by which radiation can be immunogenic is described, namely radiation-induced transcriptional upregulation of neo-antigens.
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Subject
Humans
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Antibodies, Monoclonal
CTLA-4 Antigen
Ipilimumab
Research team
Targeted Therapy
Translational Immunotherapy
Language
eng
Date accepted
2019-02-20
License start date
2019-03-06
Citation
Journal for immunotherapy of cancer, 2019, 7 (1), pp. 64 - ?
Publisher
BMC