Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis

Bernice Y Kwong; Scott J Roberts; Tobias Silberzahn; Renata B Filler; Jason H Neustadter; Anjela Galan; Swapna Reddy; William M Lin; Peter D Ellis; Cordelia F Langford; Adrian C Hayday; Michael Girardi

doi:10.1038/jid.2009.362

Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis

Bernice Y Kwong, Scott J Roberts, Tobias Silberzahn, Renata B Filler, Jason H Neustadter, Anjela Galan, Swapna Reddy, William M Lin, Peter D Ellis, Cordelia F Langford, Adrian C Hayday, Michael Girardi

Peter Gorer Department of Immunobiology

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

T-pro are tumor-infiltrating TCRalphabeta(+)CD8(+) cells of reduced cytotoxic potential that promote experimental two-stage chemical cutaneous carcinogenesis. Toward understanding their mechanism of action, this study uses whole-genome expression analysis to compare T-pro with systemic CD8(+) T cells from multiple groups of tumor-bearing mice. T-pro show an overt T helper 17-like profile (high retinoic acid-related orphan receptor-(ROR)gammat, IL-17A, IL-17F; low T-bet and eomesodermin), regulatory potential (high FoxP3, IL-10, Tim-3), and transcripts encoding epithelial growth factors (amphiregulin, Gro-1, Gro-2). Tricolor flow cytometry subsequently confirmed the presence of TCRbeta(+) CD8(+) IL-17(+) T cells among tumor-infiltrating lymphocytes (TILs). Moreover, a time-course analysis of independent TIL isolates from papillomas versus carcinomas exposed a clear association of the "T-pro phenotype" with malignant progression. This molecular characterization of T-pro builds a foundation for elucidating the contributions of inflammation to cutaneous carcinogenesis, and may provide useful biomarkers for cancer immunotherapy in which the widely advocated use of tumor-specific CD8(+) cytolytic T cells should perhaps accommodate the cells' potential corruption toward the T-pro phenotype. The data are also likely germane to psoriasis, in which the epidermis may be infiltrated by CD8(+) IL-17-producing T cells.

Original language	English
Pages (from-to)	1726 - 1736
Number of pages	11
Journal	Journal of Investigative Dermatology
Volume	130
Issue number	6
DOIs	https://doi.org/10.1038/jid.2009.362
Publication status	Published - Jun 2010

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10.1038/jid.2009.362

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Kwong, B. Y., Roberts, S. J., Silberzahn, T., Filler, R. B., Neustadter, J. H., Galan, A., Reddy, S., Lin, W. M., Ellis, P. D., Langford, C. F., Hayday, A. C., & Girardi, M. (2010). Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis. Journal of Investigative Dermatology, 130(6), 1726 - 1736. https://doi.org/10.1038/jid.2009.362

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abstract = "T-pro are tumor-infiltrating TCRalphabeta(+)CD8(+) cells of reduced cytotoxic potential that promote experimental two-stage chemical cutaneous carcinogenesis. Toward understanding their mechanism of action, this study uses whole-genome expression analysis to compare T-pro with systemic CD8(+) T cells from multiple groups of tumor-bearing mice. T-pro show an overt T helper 17-like profile (high retinoic acid-related orphan receptor-(ROR)gammat, IL-17A, IL-17F; low T-bet and eomesodermin), regulatory potential (high FoxP3, IL-10, Tim-3), and transcripts encoding epithelial growth factors (amphiregulin, Gro-1, Gro-2). Tricolor flow cytometry subsequently confirmed the presence of TCRbeta(+) CD8(+) IL-17(+) T cells among tumor-infiltrating lymphocytes (TILs). Moreover, a time-course analysis of independent TIL isolates from papillomas versus carcinomas exposed a clear association of the {"}T-pro phenotype{"} with malignant progression. This molecular characterization of T-pro builds a foundation for elucidating the contributions of inflammation to cutaneous carcinogenesis, and may provide useful biomarkers for cancer immunotherapy in which the widely advocated use of tumor-specific CD8(+) cytolytic T cells should perhaps accommodate the cells' potential corruption toward the T-pro phenotype. The data are also likely germane to psoriasis, in which the epidermis may be infiltrated by CD8(+) IL-17-producing T cells.",

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AU - Galan, Anjela

AU - Reddy, Swapna

AU - Lin, William M

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AU - Langford, Cordelia F

AU - Hayday, Adrian C

AU - Girardi, Michael

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AB - T-pro are tumor-infiltrating TCRalphabeta(+)CD8(+) cells of reduced cytotoxic potential that promote experimental two-stage chemical cutaneous carcinogenesis. Toward understanding their mechanism of action, this study uses whole-genome expression analysis to compare T-pro with systemic CD8(+) T cells from multiple groups of tumor-bearing mice. T-pro show an overt T helper 17-like profile (high retinoic acid-related orphan receptor-(ROR)gammat, IL-17A, IL-17F; low T-bet and eomesodermin), regulatory potential (high FoxP3, IL-10, Tim-3), and transcripts encoding epithelial growth factors (amphiregulin, Gro-1, Gro-2). Tricolor flow cytometry subsequently confirmed the presence of TCRbeta(+) CD8(+) IL-17(+) T cells among tumor-infiltrating lymphocytes (TILs). Moreover, a time-course analysis of independent TIL isolates from papillomas versus carcinomas exposed a clear association of the "T-pro phenotype" with malignant progression. This molecular characterization of T-pro builds a foundation for elucidating the contributions of inflammation to cutaneous carcinogenesis, and may provide useful biomarkers for cancer immunotherapy in which the widely advocated use of tumor-specific CD8(+) cytolytic T cells should perhaps accommodate the cells' potential corruption toward the T-pro phenotype. The data are also likely germane to psoriasis, in which the epidermis may be infiltrated by CD8(+) IL-17-producing T cells.

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Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis

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