Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors

Nuñez NG, Berner F, Friebel E, Unger S, Wyss N, Gomez JM, Purde MT, Niederer R, Porsch M, Lichtensteiger C, Kramer R, Erdmann M, Schmitt C, Heinzerling L, Abdou MT, Karbach J, Schadendorf D, Zimmer L, Ugurel S, Klümper N, Hölzel M, Power L, Kreutmair S, Capone M, Madonna G, Cevhertas L, Heider A, Amaral T, Hasan Ali O, Bomze D, Dimitriou F, Diem S, Ascierto PA, Dummer R, Jäger E, Driessen C, Levesque MP, van de Veen W, Joerger M, Früh M, Becher B, Flatz L (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Med Cell Press

Book Volume: 4

Pages Range: 113-129.e7

Journal Issue: 2

DOI: 10.1016/j.medj.2022.12.007

Abstract

Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. Methods: In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. Findings: When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. Conclusions: We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. Funding: This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen.

Authors with CRIS profile

Rafaela Kramer Department of Dermatology Lucie Heinzerling Department of Dermatology

Involved external institutions

University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) Klinikum der Universität München DE Germany (DE) Kantonsspital St.Gallen CH Switzerland (CH) Universitätsklinikum Essen DE Germany (DE) Universitätsspital Zürich (USZ) CH Switzerland (CH) Krankenhaus Nordwest DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" IT Italy (IT) Universitätsklinikum Tübingen DE Germany (DE)

How to cite

APA:

Nuñez, N.G., Berner, F., Friebel, E., Unger, S., Wyss, N., Gomez, J.M.,... Flatz, L. (2023). Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors. Med, 4(2), 113-129.e7. https://doi.org/10.1016/j.medj.2022.12.007

MLA:

Nuñez, Nicolas Gonzalo, et al. "Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors." Med 4.2 (2023): 113-129.e7.

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