Immune-Related Cutaneous Adverse Events Display Distinct Clinical and Molecular Characteristics, Depending on Immune Checkpoints Targeted
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Sample Processing
2.3. RNA Isolation and Sequencing
2.4. Multiplex Immunohistochemistry
2.5. Statistical Analysis
3. Results
3.1. Expression of Cytotoxicity- and Inflammation-Related Genes in ircAEs Induced by aPD1 Monotherapy Mirrors TEN, Unlike P+C Therapy
3.2. IrcAEs Induced by aPD1 Monotherapy Exhibits Stronger Immune Activation Compared to P+C Therapy
3.3. Spatial Assessment of Immune Infiltrates Reveals Distinct Cell Population Patterns in ircAEs and Cutaneous Adverse Drug Reactions
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ircAEs | immune-related cutaneous adverse events |
irAEs | immune-related adverse events |
P+C | combined immunotherapy regimen |
MPR | maculopapular rash |
TEN | toxic epidermal necrolysis |
PD1 | programmed cell death 1 |
PD-L1 | programmed cell death 1 ligand |
CTLA4 | cytotoxic T-lymphocyte antigen 4 |
KEK | Cantonal Ethics Committee of the Canton of Zurich, Switzerland |
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hs | aPD1 | P+C | MPR | TEN | |
---|---|---|---|---|---|
CD4 T-helper | 0.0000000 | 7.8935707 | 4.1027254 | 9.1723890 | 1.4977364 |
CD8 | 1.4211965 | 8.7100173 | 11.6251376 | 4.6560604 | 12.3676716 |
Granzyme B | 0.0971758 | 0.6571705 | 0.5572157 | 0.5788885 | 0.4311665 |
IL17A | 1.5851807 | 2.6123781 | 0.3999371 | 1.9213111 | 5.3736966 |
Keratinocyte | 0.3826298 | 1.6830588 | 1.0515200 | 2.2456883 | 5.1785370 |
Ml macrophage | 0.0000000 | 0.8402752 | 0.7010133 | 0.1317470 | 0.4311665 |
M2 macrophage | 0.1457637 | 0.4612456 | 0.0943672 | 1.2426142 | 1.7473591 |
Macrophage | 1.5669602 | 10.6953243 | 10.4410542 | 17.5712632 | 19.2549896 |
Neutr. gran. | 0.1457637 | 2.1646494 | 1.5233559 | 9.4169195 | 1.9459226 |
Treg | 8.5089584 | 22.1494046 | 19.5564743 | 14.6718301 | 37.8110356 |
Other | 86.1463711 | 42.1329056 | 49.9471993 | 38.3912887 | 13.9607185 |
Call | hs | aPD1 | P+C | MPR | TEN |
---|---|---|---|---|---|
CD4 T-helper | 0.0000000 | 1.0734042 | 0.2959414 | 0.4121304 | 0.0795281 |
CD8 | 0.0795042 | 0.7045840 | 1.7051860 | 0.1803070 | 0.7157532 |
Granzyme B | 0.1734637 | 0.3293258 | 1.6065389 | 0.0901535 | 0.6362251 |
IL17A | 0.6017021 | 0.3091041 | 0.2113867 | 0.1442456 | 1.9285572 |
Keratinocyte | 80.1618994 | 95.9794184 | 95.1803833 | 98.9585122 | 93.7239048 |
M2 macrophage | 0.0216830 | 0.0259994 | 0.0000000 | 0.0257581 | 0.0000000 |
Macrophage | 0.0000000 | 0.2729938 | 0.0422773 | 0.1030326 | 1.5905627 |
Treg | 0.5637569 | 1.3051703 | 0.9582864 | 0.0858605 | 1.3254689 |
Other | 18.3979907 | 0.0000000 | 0.0000000 | 0.0000000 | 0.0000000 |
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Kraehenbuehl, L.; Winkelbeiner, N.; Turko, P.; Staeger, R.; Ghosh, A.; Kaiser, V.; Stadler, P.-C.; Nordmann, T.M.; Brüggen, M.-C.; Levesque, M.P.; et al. Immune-Related Cutaneous Adverse Events Display Distinct Clinical and Molecular Characteristics, Depending on Immune Checkpoints Targeted. Cancers 2025, 17, 1992. https://doi.org/10.3390/cancers17121992
Kraehenbuehl L, Winkelbeiner N, Turko P, Staeger R, Ghosh A, Kaiser V, Stadler P-C, Nordmann TM, Brüggen M-C, Levesque MP, et al. Immune-Related Cutaneous Adverse Events Display Distinct Clinical and Molecular Characteristics, Depending on Immune Checkpoints Targeted. Cancers. 2025; 17(12):1992. https://doi.org/10.3390/cancers17121992
Chicago/Turabian StyleKraehenbuehl, Lukas, Nicola Winkelbeiner, Patrick Turko, Ramon Staeger, Adhideb Ghosh, Vivienn Kaiser, Pia-Charlotte Stadler, Thierry M. Nordmann, Marie-Charlotte Brüggen, Mitchell P. Levesque, and et al. 2025. "Immune-Related Cutaneous Adverse Events Display Distinct Clinical and Molecular Characteristics, Depending on Immune Checkpoints Targeted" Cancers 17, no. 12: 1992. https://doi.org/10.3390/cancers17121992
APA StyleKraehenbuehl, L., Winkelbeiner, N., Turko, P., Staeger, R., Ghosh, A., Kaiser, V., Stadler, P.-C., Nordmann, T. M., Brüggen, M.-C., Levesque, M. P., Contassot, E., French, L. E., Dummer, R., & Meier-Schiesser, B. (2025). Immune-Related Cutaneous Adverse Events Display Distinct Clinical and Molecular Characteristics, Depending on Immune Checkpoints Targeted. Cancers, 17(12), 1992. https://doi.org/10.3390/cancers17121992