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

作者：Strobel S B; Safferling K; Lahrmann B; Hoffmann J H; Enk A H; Hadaschik E N; Grabe N; Lonsdorf A S^*

来源：British Journal of Dermatology, 2018, 179(2): 405-412.

DOI：10.1111/bjd.16477

BackgroundThe 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.
ObjectivesTo 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.
MethodsWe 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.
ResultsThe 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.
ConclusionsImmune 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.
What's already known about this topic?
Long-term immunosuppression is a major risk factor for skin carcinogenesis. Cutaneous squamous cell carcinoma (SCC) arising in immunosuppressed organ transplant recipients (OTRs) shows a considerably increased incidence and more aggressive disease progression compared with that in immunocompetent patients. The inflammatory tumour microenvironment, in particular the composition and localization of infiltrating immune cells, may alter tumour behaviour and affect the clinical course of several types of cancer, including SCC.
What does this study add?
Long-term iatrogenic immunosuppression markedly disturbs the composition and microanatomical distribution of intra- and peritumoral immune infiltrates of SCC. The overall reduced density of infiltrating adaptive immune cells, particularly reduced CD4(+) infiltrates at the invasive margin of SCC, may contribute to the aggressiveness of SCC arising in OTRs. The cutaneous CD20 B-cell compartment at the site of a growing SCC is significantly affected by systemic immunosuppression.
What is the translational message?
Objective analysis of phenotype and specific microanatomical distribution of infiltrating immune cells in SCC and surrounding skin by high-resolution semiautomated microscopy with integration of associated histopathological and clinical parameters provides insight into skin's normal functions and the impact of immunosuppression. SCC arising in OTRs may serve as a model cancer in which to study defective immune cell homing and function that may underlie altered immune responses to several human cancers.
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• 出版日期2018-8