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. 2025 Sep 18:S0190-9622(25)02830-0.
doi: 10.1016/j.jaad.2025.09.042. Online ahead of print.

Impact of immunosuppression on cutaneous squamous cell carcinoma outcomes

Jason C Klein  1 , Kathryn T Shahwan  2 , Ursa Bezan Petric  3 , Teja Mallela  4 , Lindsey Voller  5 , Emily Ruiz  6 , Nina Ran  6 , Emily E Granger  7 , Shlomo Koyfman  8 , Allison Vidimos  9 , Ashley Wysong  10 , Kelsey Hirotsu  5 , John A Carucci  11 , Joi B Carter  12 , Javier Cañueto  13 , Fabio Muradás Girardi  14 , Aaron R Mangold  15 , David G Brodland  16 , John A Zitelli  16 , Tyler J Willenbrink  16 , William Lotter  17 , Vincent Jeanselme  18 , Melica Nikahd  19 , Rajiv I Nijhawan  20 , Divya Srivastava  20 , David R Carr  21
Affiliations

Impact of immunosuppression on cutaneous squamous cell carcinoma outcomes

Jason C Klein et al. J Am Acad Dermatol. .

Abstract

Background: Immunosuppression is associated with a higher risk of developing cutaneous squamous cell carcinoma (CSCC) and more aggressive tumors, but its role as an independent predictor of poor outcomes remains unclear.

Objective: To determine whether immunosuppression independently predicts poor outcomes in CSCC.

Methods: This was a retrospective cohort study with pooled data from 12 international centers. Demographics, immunosuppression status, tumor characteristics, treatment, and outcomes were collected. Univariable and multivariable marginal Fine and Gray competing risk analyses were performed. Subgroup multivariable analyses were performed on the organ transplant and chronic lymphocytic leukemia cohorts.

Results: A total of 11,930 patients with 18,760 tumors (14,766 in immunocompetent and 3994 in immunosuppressed) were included. Immunosuppressed patients had a higher prevalence of high-risk tumor features and poor disease outcomes. On multivariable analysis, immunosuppression was independently associated with local recurrence (LR), distant metastasis, disease-specific death (DSD), and major poor outcomes. Organ transplantation was predictive of LR, distant metastasis, and DSD, whereas chronic lymphocytic leukemia independently predicted LR, DSD, and major poor outcomes.

Limitations: A retrospective design, potential for data heterogeneity.

Conclusions: Immunosuppression is an independent risk factor for major poor outcomes in CSCC and should be included in risk nomograms.

Keywords: chronic lymphocytic leukemia; cutaneous squamous cell carcinoma; immunosuppression; poor outcomes; solid organ transplant.

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Conflict of interest statement

Conflicts of interest Dr Ruiz serves as a consultant for Regeneron Inc., Checkpoint Therapeutic, Feldan Pharmaceuticals, and Merck Pharmaceuticals. She serves as a principal investigator/co-investigator for the following companies: Regeneron (PI/Co-I), Merck (Co-I), and Castle Biosciences (PI/Co-I). She is on the Board of Directors of the Skin Cancer Outcomes Consortium (SCOUT). Dr Carr is an investigator for Regeneron, no direct funds; Dr Cañueto’s grants to the institution are from Sanofi/Regeneron, Castle Biosciences; lecture honoraria: Sanofi, Almirall, AbbVie, Regeneron, and Sun Pharma; payment for expert testimony: Sanofi, Regeneron, Almirall; support for attending meetings: Pfizer, Almirall, Lilly, and Castle Biosciences; advisory board: Almirall, Sanofi, Regeneron, Kyowa, Roche, and InflaRx; funding support by the Gerencia Regional de Salud de Castilla y León (GRS2549/A/22) and by the Instituto de Salud Carlos III (PI21/01,207), cofinanced by the European Union. Dr Mangold consulted for Phlecs BV, Kyowa, Eli Lilly, Momenta, UCB, and Regeneron in the past, greater than 24 months ago. He has consulted for Incyte, Soligenix, Clarivate, Argenyx, and Bristol Myers Squibb in the past, less than 12 months ago. He consults for Nuvig, Tourmaline Bio, Janssen, and Boehringer Ingelheim currently. He consults for Regeneron and Pfizer currently with payments to the institution. He has grant support from Kyowa, Miragen, Regeneron, Corbus, Pfizer, Incyte, Eli Lilly, Argenx, Palvella, AbbVie, Priovant, Bristol Myers Squibb, and Merck in the last 24 months. Beyond 24 months, grant support has come from Sun Pharma, Elorac, Novartis, and Janssen. He has received royalties from Adelphi Values and Clarivate. His current patents include Methods and Materials for assessing and treating cutaneous squamous cell carcinoma (PCT/US2023/078,902), Use of Oral Jaki in Lichen Planus-PCT/US2024/020,149; and Topical Ruxolitinib in Lichen Planus-PCT/US2021/053,149, 2023-520,085, & 21,805,700.8, respectively. Methods and Materials for Treating Lichen Planopilaris (registration number: 53,103), Machine-Learning Models for Tumor Grading Using Rank-Aware Contextual Reasoning on Whole Slide Images (63/616,287). Dr Carucci receives funding for investigator-initiated basic science research from Regeneron and is a PI for a clinical trial sponsored by Regeneron. Dr Koyfman is on the advisory board (paid): Merck, BMS, Regeneron, and Galera Therapeutics; advisory board (unpaid): Castle Biosciences; research support: Castle Biosciences, Merck, BMS, Regeneron; honoraria: UpToDate. Dr Vidimos receives research support from Castle; advisory board - Inhibitor Therapeutics; honoraria - Up to Date. Dr Wysong receives an institutional research grant from Castle Biosciences. The other authors have no conflicts of interest to declare.

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