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

S.B. Strobel, K. Safferling, B. Lahrmann, J.H. Hoffmann, A.H. Enk, E.N. Hadaschik, N. Grabe, A.S. Lonsdorf

The inflammatory tumor microenvironment is crucial for effective tumor control and long-term immunosuppression has been identified as a major risk factor for skin carcinogenesis. In solid organ transplant recipients (OTR) undergoing long-term pharmacologic immunosuppression an increased incidence of cutaneous squamous cell carcinoma (SCC) and more aggressive tumor growth compared to immunocompetent patients (IC) has been reported. To determine the density and phenotype of immune cells infiltrating SCC and surrounding skin in OTR, and to characterize the microanatomical distribution patterns in comparison to IC. We analyzed immune cell infiltrates within SCC and at defined regions of interest (ROI) of tumor- surrounding skin in formalin-fixed paraffin-embedded (FFPE) tissue of 20 renal transplant patients and 18 carefully matched IC by high-resolution semi-automated microscopy on complete tissue sections stained for CD4, CD8, CD20 and CD68. The overall immune cell density of SCC arising in OTR was significantly reduced compared to IC. Particularly CD4+ infiltrates at the directly invasive margin and tumor vicinity, intratumoral CD8+ T cell densities and the overall density of CD20+ tumor-infiltrating B cells (TIL-B) were significantly reduced in tissue of OTR. Immune cells infiltrates within SCC and at defined ROI of tumor-surrounding skin in OTR differ markedly in their composition and microanatomical distribution compared to tumors arising in IC. 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. This article is protected by copyright. All rights reserved.