Radiotherapy enhances responses of lung cancer to CTLA-4 blockade.
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Embargo End Date
ICR Authors
Authors
Wilkins, A
McDonald, F
Harrington, K
Melcher, A
McDonald, F
Harrington, K
Melcher, A
Document Type
Journal Article
Date
2019-03-06
Date Accepted
2019-02-20
Abstract
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.
Citation
Journal for immunotherapy of cancer, 2019, 7 (1), pp. 64 - ?
Source Title
Publisher
BMC
ISSN
2051-1426
eISSN
2051-1426
Research Team
Targeted Therapy
Translational Immunotherapy
Translational Immunotherapy