Altered density, composition and microanatomical distribution of infiltrating immune cells in cutaneous squamous cell carcinoma of organ transplant recipients

Abstract

Background: The inflammatory tumour microenvironment is crucial for effective tumour control, and long-term immunosuppression has been identified as a major risk factor for skin carcinogenesis. In solid organ transplant recipients (OTRs) undergoing long-term pharmacological immunosuppression, an increased incidence of cutaneous squamous cell carcinoma (SCC) and more aggressive tumour growth compared with immunocompetent patients has been reported. Objectives: To determine the density and phenotype of immune cells infiltrating SCC and surrounding skin in OTRs, and to characterize the microanatomical distribution patterns in comparison with immunocompetent patients. Methods: We analysed immune cell infiltrates within SCC and at defined regions of interest (ROIs) of tumour-surrounding skin in formalin-fixed paraffin-embedded tissue of 20 renal transplant patients and 18 carefully matched immunocompetent patients by high-resolution semiautomated microscopy on complete tissue sections stained for CD4, CD8, CD20 and CD68. Results: The overall immune cell density of SCC arising in OTRs was significantly reduced compared with immunocompetent patients. Particularly CD4+ infiltrates at the directly invasive margin and tumour vicinity, intratumoral CD8+ T-cell densities and the overall density of CD20+ tumour-infiltrating B cells were significantly reduced in the tissue of OTRs. Conclusions: Immune cell infiltrates within SCC and at defined ROIs of tumour-surrounding skin in OTRs differ markedly in their composition and microanatomical distribution compared with tumours arising in immunocompetent patients. Our findings substantially broaden the understanding of how long-term systemic immunosuppression modulates the local inflammatory microenvironment in the skin and at the site of invasive SCC.