Molecular Analysis of Tumor-Promoting CD8(+) T Cells in Two-Stage Cutaneous Chemical Carcinogenesis

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

来源：Journal of Investigative Dermatology, 2010, 130(6): 1726-1736.

DOI：10.1038/jid.2009.362

T-pro are tumor-infiltrating TCR alpha beta(+)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)gamma t, 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 TCR beta(+) 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.

• 出版日期2010-6