ABSTRACT Background As solid organ transplantation becomes more prevalent, more patients are living on long‐term immunosuppression, greatly increasing the risk of cutaneous squamous cell carcinoma (cSCC). Although significant improvements have been achieved in the treatment of cSCC, further studies are needed to identify the specific protein expression profile in this patient cohort. Objectives The goal of this systematic review is to summarise the data on biomarker and mRNA profiles in cSCC. Such profiles may influence tumour differentiation, treatment response and may offer predictive value to the multidisciplinary team. Methods A systematic review was performed in accordance with PRISMA guidelines. Databases searched were PubMed, Scopus and Embase. Results Thirty‐four studies totalling 4644 total patients and 3754 organ transplant recipients (OTRs) with immunohistochemically analysed cSCC were included in the final analysis. Ninety‐one biomarkers significantly differed ( p < 0.05) from normal skin or autologous skin prior to specific immunosuppressive treatment. Among studies in which specific data were available, the most common immunosuppressant was cyclosporine (16/21 studies, 628 patients). All studies which reported demographic data included renal transplant patients (27/38). Among others, CD8+ T cells were significantly increased in transplant SCC versus immunocompetent SCC and normal skin (42.22 ± 8.38 cells/µm 2 × 10 5 versus 6.88 ± 2.56 cells/µm 2 × 10 5 , p < 0.05) and OTRs had decreased numbers of CD4+ Th1 cells compared with immunocompetent patients (15.1% + 2.3% vs. 25.1% + 3.2%, respectively; p < 0.05). No studies focussed on B‐cell‐specific markers. Conclusions While there exists a plethora of individual studies profiling individual tissue markers, a focus should remain on collating these results in order to adequately direct further efforts in this field. With some newly published papers highlighting the role of B‐cells in the tumour microenvironment of head and neck squamous cell carcinoma, further research may be warranted amongst this chronically immunosuppressed cohort to form a comprehensive suite of tSCC prognostic indicators.
Murray et al. (2026) studied this question.