Immunity against Non-Melanoma Skin Cancer and the Effect of Immunosuppressive Medication on Non-Melanoma Skin Cancer Risk in Solid Organ Transplant Recipients

Sep 24, 2026

Uploaded by Grenda

Non-melanoma skin cancers (NMSCs) occur frequently in the Caucasian population and create a sustained burden for health care. Risk is driven by ultraviolet radiation, ethnicity, and—critically—immunosuppression. Solid organ transplant recipients experience higher NMSC incidence than immunocompetent individuals because immunosuppressive medication alters antitumor defense. Calcineurin inhibitors and purine analogues increase NMSC risk, whereas mTOR inhibitors do not, likely via distinct immune pathway effects. This review summarizes immune mechanisms against cutaneous squamous cell carcinoma and basal cell carcinoma and explains how different immunosuppressants target immune compartments.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Risk factors for non-melanoma skin cancer

Immunity against NMSC

Innate immunity against NMSC

Dendritic cells

Overview of immune cells in immunosurveillance

cells Review Immunity against Non-Melanoma Skin Cancer and the Effect of Immunosuppressive Medication on Non-Melanoma Skin Cancer Risk in Solid Organ Transplant Recipients Dixie Bakker 1,2, Walbert J. Bakker 1,2, Marcel W. Bekkenk 1,2,3 and Rosalie M. Luiten 1,2, * Citation: Bakker, D.; Bakker, W.J.; Bekkenk, M.W.; Luiten, R.M. Immunity against Non-Melanoma Skin Cancer and the Effect of Immunosuppressive Medication on Non-Melanoma Skin Cancer Risk in Solid Organ Transplant Recipients. Cells 2023, 12, 2441. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cells12202441](10.3390/cells12202441) Academic Editors: Phyu P. Aung and Dinesh Pradhan Received: 16 August 2023 Revised: 22 September 2023 Accepted: 10 October 2023 Published: 11 October 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Dermatology, Netherlands Institute for Pigment Disorders, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands 2 Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, 1081 HV Amsterdam, The Netherlands 3 Amsterdam University Medical Centers, VU University of Amsterdam, 1081 HV Amsterdam, The Netherlands * Correspondence: [r.m.luiten@amsterdamumc.nl](r.m.luiten@amsterdamumc.nl) Abstract: Non-melanoma skin cancers (NMSCs) occur frequently in the Caucasian population and are considered a burden for health care. Risk factors include ultraviolet (UV) radiation, ethnicity and immunosuppression. The incidence of NMSC is signiﬁcantly higher in solid organ transplant recipients (SOTRs) than in immunocompetent individuals, due to immunosuppressive medication use by SOTRs. While the immunosuppressive agents, calcineurin inhibitors and purine analogues increase the incidence of NMSC in transplant recipients, mTOR inhibitors do not. This is most likely due to the different immunological pathways that are inhibited by each class of drug. This review will focus on what is currently known about the immune response against cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), two of the main types of NMSC. Furthermore, we will describe the different classes of immunosuppressants given to SOTRs, which part of the immune system they target and how they can contribute to NMSC development. The risk of developing NMSC in SOTRs is the result of a combination of inhibiting immunological pathways involved in immunosurveillance against NMSC and the direct (pro/anti) tumor effects of immunosuppressants. Keywords: non-melanoma skin cancer; cancer immunity; transplantation; immune suppression 1. Introduction Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most frequent types of cancers among Caucasians. While overall mortality rates of these cancers are low, the steadily increasing number of cases continues to cause burden to society and health care. Risk factors for developing NMSC include chronic exposure to ultraviolet radiation (UVR), age, ethnicity and family history of skin cancer [1] . More than 90% of BCC show the upregulation of the Hedgehog pathway, involving the Patched 1 (PTCH1) gene and smoothened (SMO) and glioma-associated (GLI) oncogenes. The Hedgehog pathway is implicated in self-renewal, survival and angiogenesis and can drive a cancer stem phenotype. Although BCC rarely metastasize, local invasion and tissue destruction cause high morbidity. In cSCC, a more diverse (UV-induced) gene mutational proﬁle has been found, including tumor suppressors, epigenetic regulators and DNA repair pathways, leading to a high neoantigen b

FAQs

Why is the incidence of non-melanoma skin cancer higher in solid organ transplant recipients?

Because transplant recipients require long-term immunosuppressive medication, which increases NMSC incidence compared with immunocompetent individuals. The review highlights immunosuppressive effects on immune surveillance as a key driver.

Do all immunosuppressive drug classes affect non-melanoma skin cancer risk in the same way?

No. Calcineurin inhibitors and purine analogues increase NMSC risk, while mTOR inhibitors have been shown to reduce risk. The review links these differences to distinct immunological pathways inhibited by each drug class.

Which immune responses and cancer types does the review focus on?

The review focuses on immune responses against cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), two main NMSC types. It also describes how immunosuppressants target parts of the immune system and contribute to NMSC development.

Sep 24, 2026

Uploaded by Grenda