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Increased Tc22 and Treg/CD8 ratio contribute to aggressive growth of transplant associated squamous cell carcinoma.

Zhang S, Fujita H, Mitsui H, Yanofsky VR, Fuentes-Duculan J, Pettersen JS, Suárez-Fariñas M, Gonzalez J, Wang CQ, Krueger JG, Felsen D, Carucci JA - PLoS ONE (2013)

Bottom Line: SCC and TSCC are both associated with significantly higher numbers of CD3(+) and CD8(+) T cells compared to normal skin.TSCC, however, had a higher percentage of IL-22 producing CD8(+) T cells compared to SCC.Diminished cytotoxic T cell function in TSCC due to decreased CD8/T-reg ratio may permit tumor progression.

View Article: PubMed Central - PubMed

Affiliation: Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York, New York, United States of America.

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.

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Related in: MedlinePlus

IL-22 expression is increased in SCC, TSCC, and juxtatumoral skin.The relative mRNA expression of IL-22 relative to Human Acidic Ribosomal Protein (HARP) in normal (n = 9), SCC (n = 9), SCC peritumoral (n = 9), TSCC (n = 7), and TSCC peritumoral tissue (n = 7). Data expressed as mean relative mRNA expression ± standard error. Asterisks (*) indicate statistical significance, where *P<0.05.
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pone-0062154-g004: IL-22 expression is increased in SCC, TSCC, and juxtatumoral skin.The relative mRNA expression of IL-22 relative to Human Acidic Ribosomal Protein (HARP) in normal (n = 9), SCC (n = 9), SCC peritumoral (n = 9), TSCC (n = 7), and TSCC peritumoral tissue (n = 7). Data expressed as mean relative mRNA expression ± standard error. Asterisks (*) indicate statistical significance, where *P<0.05.

Mentions: To further assess the expression of IL-22 within the tissue, we performed reverse transcriptase-PCR (RT-PCR) on mRNA extracted from SCC, TSCC, their respective adjacent non-tumor bearing skin and normal skin from healthy volunteers. RT-PCR analysis showed that mean IL-22 mRNA expression was increased approximately 30-fold in SCC and 8-fold in TSCC compared to normal skin (p<0.05; Figure 4). Even more striking, there was significantly increased expression of IL-22 in the peritumoral regions of SCC and TSCC compared to normal skin. IL-22 mRNA was increased 111-fold in SCC and 97-fold in TSCC peritumoral skin. In general, we found that the entire family of IL-10 cytokines including IL-10, IL-19, IL-20, IL-22 and IL-24 was increased in tumor compared to normal skin.


Increased Tc22 and Treg/CD8 ratio contribute to aggressive growth of transplant associated squamous cell carcinoma.

Zhang S, Fujita H, Mitsui H, Yanofsky VR, Fuentes-Duculan J, Pettersen JS, Suárez-Fariñas M, Gonzalez J, Wang CQ, Krueger JG, Felsen D, Carucci JA - PLoS ONE (2013)

IL-22 expression is increased in SCC, TSCC, and juxtatumoral skin.The relative mRNA expression of IL-22 relative to Human Acidic Ribosomal Protein (HARP) in normal (n = 9), SCC (n = 9), SCC peritumoral (n = 9), TSCC (n = 7), and TSCC peritumoral tissue (n = 7). Data expressed as mean relative mRNA expression ± standard error. Asterisks (*) indicate statistical significance, where *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646982&req=5

pone-0062154-g004: IL-22 expression is increased in SCC, TSCC, and juxtatumoral skin.The relative mRNA expression of IL-22 relative to Human Acidic Ribosomal Protein (HARP) in normal (n = 9), SCC (n = 9), SCC peritumoral (n = 9), TSCC (n = 7), and TSCC peritumoral tissue (n = 7). Data expressed as mean relative mRNA expression ± standard error. Asterisks (*) indicate statistical significance, where *P<0.05.
Mentions: To further assess the expression of IL-22 within the tissue, we performed reverse transcriptase-PCR (RT-PCR) on mRNA extracted from SCC, TSCC, their respective adjacent non-tumor bearing skin and normal skin from healthy volunteers. RT-PCR analysis showed that mean IL-22 mRNA expression was increased approximately 30-fold in SCC and 8-fold in TSCC compared to normal skin (p<0.05; Figure 4). Even more striking, there was significantly increased expression of IL-22 in the peritumoral regions of SCC and TSCC compared to normal skin. IL-22 mRNA was increased 111-fold in SCC and 97-fold in TSCC peritumoral skin. In general, we found that the entire family of IL-10 cytokines including IL-10, IL-19, IL-20, IL-22 and IL-24 was increased in tumor compared to normal skin.

Bottom Line: SCC and TSCC are both associated with significantly higher numbers of CD3(+) and CD8(+) T cells compared to normal skin.TSCC, however, had a higher percentage of IL-22 producing CD8(+) T cells compared to SCC.Diminished cytotoxic T cell function in TSCC due to decreased CD8/T-reg ratio may permit tumor progression.

View Article: PubMed Central - PubMed

Affiliation: Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York, New York, United States of America.

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.

Show MeSH
Related in: MedlinePlus