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

Lansink Rotgerink, Laura; Felchle, Hannah; Feuchtinger, Annette; Nefzger, Sophie M; Walther, Caroline N; Gissibl, Julia; Steiger, Katja; Schmid, Thomas E; Heidegger, Simon; Combs, Stephanie E; Fischer, Julius C

doi:10.1002/path.5989

journal article

Title:: Experimental investigation of skin toxicity after immune checkpoint inhibition in combination with radiation therapy.
Document type:: Journal Article; Research Support, Non-U.S. Gov't
Author(s):: Lansink Rotgerink, Laura; Felchle, Hannah; Feuchtinger, Annette; Nefzger, Sophie M; Walther, Caroline N; Gissibl, Julia; Steiger, Katja; Schmid, Thomas E; Heidegger, Simon; Combs, Stephanie E; Fischer, Julius C
Abstract:: 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 among the most common adverse events after monotherapy with either ICIs or RT. So far, little is known about interindividual differences for 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 the 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. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Journal title abbreviation:: J Pathol
Year:: 2022
Journal volume:: 258
Journal issue:: 2
Pages contribution:: 189-198
Fulltext / DOI:: doi:10.1002/path.5989
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/35830288
Print-ISSN:: 0022-3417
TUM Institution:: Institut für Allgemeine Pathologie und Pathologische Anatomie; Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie; Klinik und Poliklinik für RadioOnkologie und Strahlentherapie
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