Abstract
Immune suppressed organ transplant recipients suffer increased morbidity and mortality from primary cutaneous SCC. We studied tumor microenvironment in transplant-associated SCC (TSCC), immune-competent SCC and normal skin by IHC, IF and RT-PCR on surgical discard. We determined T cell polarization in TSCC and SCC by intracellular cytokine staining of T cell crawl outs from human skin explants. We studied the effects of IL-22, an inducer of keratinocyte proliferation, on SCC proliferation in vitro. SCC and TSCC are both associated with significantly higher numbers of CD3(+) and CD8(+) T cells compared to normal skin. TSCC showed a higher proportion of Foxp3(+) T regs to CD8(+) T cells compared to SCC and a lower percentage of IFN-γ producing CD4(+) T cells. TSCC, however, had a higher percentage of IL-22 producing CD8(+) T cells compared to SCC. TSCC showed more diffuse Ki67 and IL-22 receptor (IL-22R) expression by IHC. IL-22 induced SCC proliferation in vitro despite serum starvation. Diminished cytotoxic T cell function in TSCC due to decreased CD8/T-reg ratio may permit tumor progression. Increased IL-22 and IL-22R expression could accelerate tumor growth in transplant patients. IL-22 may be an attractive candidate for targeted therapy of SCC without endangering allograft survival.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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CD3 Complex / metabolism
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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Carcinoma, Squamous Cell / etiology
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Carcinoma, Squamous Cell / immunology*
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology*
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Cell Count
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Forkhead Transcription Factors / metabolism
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / immunology
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Humans
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Immunocompetence / immunology
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Interleukin-22
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Interleukins / pharmacology
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Organ Transplantation / adverse effects*
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Phosphoproteins / metabolism
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Receptors, Interleukin / metabolism
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STAT3 Transcription Factor / metabolism
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Skin / cytology
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Skin / immunology
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Skin / pathology
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Skin Neoplasms / immunology
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Skin Neoplasms / pathology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology
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T-Lymphocytes, Regulatory / cytology*
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology
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Th1 Cells / cytology
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Th1 Cells / drug effects
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Th1 Cells / immunology
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Tumor Microenvironment / drug effects
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Tumor Microenvironment / immunology
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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CD3 Complex
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FOXP3 protein, human
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Forkhead Transcription Factors
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Interleukins
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Phosphoproteins
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Receptors, Interleukin
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STAT3 Transcription Factor
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interleukin-22 receptor