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Lansink Rotgerink, L.* ; Felchle, H.* ; Feuchtinger, A. ; Nefzger, S.M.* ; Walther, C.N.* ; Gissibl, J.* ; Steiger, K.* ; Schmid, T.E. ; Heidegger, S.* ; Combs, S.E. ; Fischer, J.C.*

Experimental investigation of skin toxicity after immune checkpoint inhibition in combination with radiation therapy.

J. Pathol. 258, 189-198 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, structured knowledge to mitigate a patient's specific risk of developing adverse events are limited. Nevertheless, there is an exponential growth of clinical studies combining conventional therapies such as radiation therapy (RT) with ICIs. Cutaneous reactions are amongst the most common adverse events after monotherapy with either ICIs or RT. So far, little is known about inter-individual differences in the risk of developing severe tissue toxicity after the combination of RT with ICIs, and the underlying biological mechanisms are ill defined. We used experimental models of RT-induced skin injury to analyze skin toxicity after simultaneous application of ICIs. We compared different RT regimens such as fractionated or stereotactic RT with varying dose intensity. Strikingly, we found that simultaneous application of RT and ICIs did not significantly aggravate acute skin injury in two different mouse strains. Detailed examination of long-term tissue damage of the skin revealed similar signs of epidermal hyperplasia, dermal fibrosis, and adnexal atrophy. In summary, we here present the first experimental study demonstrating excellent safety profiles of concurrent treatment with RT and ICIs. These findings will help to interpret the development of adverse events of the skin after radioimmunotherapy and guide the design of new clinical trials and clinical decision making in individual cases. This article is protected by copyright. All rights reserved.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Adnexal Atrophy ; Dermal Fibrosis ; Epidermal Hyperplasia ; Immune Checkpoint Inhibition ; Immune-related Adverse Events ; Radiation Therapy ; Radiodermatitis ; Skin Toxicity
ISSN (print) / ISBN 0022-3417
e-ISSN 1096-9896
Journal Journal of Pathology, The
Quellenangaben Volume: 258, Issue: 2, Pages: 189-198 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CF Pathology & Tissue Analytics (CF-PTA)
Institute of Radiation Medicine (IRM)
Grants Faculty of Medicine, Munich University of Technology
Friedrich Naumann Stiftung
Deutsche Krebshilfe
Technische Universität München
Else Kroner-Fresenius-Stiftung
Deutsche Forschungsgemeinschaft
European Commission
Bristol Myers‐Squibb and Novartis