title: Density and Polarization States of Tumor-Associated Macrophages in Human Cutaneous Squamous Cell Carcinomas Arising in Solid Organ Transplant Recipients.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The authors examined whether TAM density and polarization states differ between SOTRs and nontransplant individuals.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *Yale Transplant Dermatology Clinic, Yale University School of Medicine, New Haven, Connecticut; Departments of †Internal Medicine, Section of Medical Oncology, ‡Dermatology, and §Pathology, Yale University School of Medicine, New Haven, Connecticut; ‖Yale-New Haven Transplantation Center, Yale University School of Medicine, New Haven, Connecticut; ¶Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Nika
authors.initials: N
authors.lastname: Cyrus
authors.forename: Christine
authors.initials: C
authors.lastname: Mai-Anh Bui
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Yao
authors.forename: Lucinda Liu
authors.initials: LL
authors.lastname: Kohn
authors.forename: Anjela
authors.initials: A
authors.lastname: Galan
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Rhebergen
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Colegio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001119:Arginase / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D002278:Carcinoma in Situ / Q000276:immunology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D002452:Cell Count; D016764:Cell Polarity; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D012878:Skin Neoplasms / Q000276:immunology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001119:Arginase; D019013:CD40 Antigens; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C574619:ARG1 protein, human