title: Increased Tc22 and Treg/CD8 ratio contribute to aggressive growth of transplant associated squamous cell carcinoma.
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.
authors.affiliation: Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York, New York, United States of America.
authors.forename: Shali
authors.initials: S
authors.lastname: Zhang
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.forename: Valerie R
authors.initials: VR
authors.lastname: Yanofsky
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Julia S
authors.initials: JS
authors.lastname: Pettersen
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Juana
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Claire Q F
authors.initials: CQ
authors.lastname: Wang
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Diane
authors.initials: D
authors.lastname: Felsen
authors.forename: John A
authors.initials: JA
authors.lastname: Carucci
mesh_terms: D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007121:Immunocompetence / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology; D016377:Organ Transplantation / Q000009:adverse effects*; D010750:Phosphoproteins / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D017252:CD3 Complex; D051858:Forkhead Transcription Factors; D007378:Interleukins; D010750:Phosphoproteins; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C418974:FOXP3 protein, human; C415369:interleukin-22 receptor