Density and Polarization States of Tumor-Associated Macrophages in Human Cutaneous Squamous Cell Carcinomas Arising in Solid Organ Transplant Recipients.

Abstract

Solid organ transplant recipients (SOTRs) are 100 times more likely to develop cutaneous squamous cell carcinoma (SCC) with greater metastatic propensity compared with the general population, likely due to chronic immunosuppression and adverse drug effects on keratinocytes. Tumor-associated macrophages (TAMs) play critical roles in malignancies, either aiding in eradication of malignant cells or promoting tumor growth. The authors examined whether TAM density and polarization states differ between SOTRs and nontransplant individuals. The authors obtained normal skin, SCC in situ (SCCis), and SCC from SOTRs and nontransplant patients (N = 45) and stained with macrophage marker CD68, M1 marker CD40, and M2 marker arginase-1. The authors report a significantly higher density of TAMs in both SCCis and SCC. The intratumoral macrophage infiltration in SCCis from SOTR was significantly decreased compared with nontransplant patients. Tumor-associated macrophages in SCCis and SCC displayed both M1 and M2 polarization, and M2 activation levels were significantly lower in SCC from SOTR. Tumor-associated macrophages are present in early carcinogenesis and may play a critical role in the transition from SCCis to SCC, before invasion of the basement membrane by tumor cells. The intratumoral macrophage density in early stages of tumor development is significantly affected in SOTR.