Cutaneous antigen presenting cells (APC) play a critical role in the initiation of T-cell mediated immune responses in the skin. The hypothesis to development of systemic immunity against skin cancers and thereby contribute to the outcome of the host-tumor interaction. This hypothesis is based on recent studies indicating that damage to the antigen presenting Langerhans cells in the skin resulting from ultraviolet (UV) irradiation prevents the development of T-cell mediated immunity to haptens applied to the irradiated skin and results in the development of hapten-specific suppressor T lymphocytes. Specifically, they will investigate whether impairing the activity of cutaneous antigen presenting cells by exposure of mice to UV radiation interferes with the development of systemic immunity to transplanted skin cancers or alters the pathogenesis of primary skin cancer in murine tumor models. In the transplanted tumor model, UV-induced progressor skin tumors are implanted into the pinna of the ear of syngeneic normal or UV-irradiated mice. The antigen presenting activity of cells recovered from the draining lymph nodes will be assessed using in vivo and in vitro assays of specific anti-tumor immunity, and the effect of UV-irradiation on tumor growth and progression will be determined. In the primary tumor model, they will investigate the effect of local UV-irradiation on the induction and progression of skin cancers that develop in transgenic mice carrying the bovine papilloma virus genome. In addition, they propose to continue their studies on the mechanism of cutaneous sensitization and its alteration by UV radiation using contact hypersensitivity to a fluorescent hapten as a model system.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Pathology B Study Section (PTHB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas MD Anderson Cancer Center
Other Domestic Higher Education
United States
Zip Code
Ma, Lisa J; Guzman, Esther A; DeGuzman, Ariel et al. (2007) Local cytokine levels associated with delayed-type hypersensitivity responses: modulation by gender, ovariectomy, and estrogen replacement. J Endocrinol 193:291-7
Maeda, Yutaka; Hwang-Verslues, Wendy W; Wei, Gang et al. (2006) Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4alpha (HNF4alpha) gene. Biochem J 400:303-13
Ma, Lisa J; Guzman, Esther A; DeGuzman, Ariel et al. (2006) Unexpected effects of UVB in IL-10 transgenic mice: normalization of contact hypersensitivity response. Arch Dermatol Res 297:417-20
Guzman, E A; Chen, Y-H; Langowski, J L et al. (2005) Abrogation of delayed type hypersensitivity response to Candida albicans produced by a molecular mimic of phosphorylated prolactin. J Neuroimmunol 170:31-40
Nishigori, C; Yarosh, D; O'Connor, A et al. (1998) HindIII liposomes suppress delayed-type hypersensitivity responses in vivo and induce epidermal IL-10 in vitro. J Immunol 161:2684-91
Vink, A A; Moodycliffe, A M; Shreedhar, V et al. (1997) The inhibition of antigen-presenting activity of dendritic cells resulting from UV irradiation of murine skin is restored by in vitro photorepair of cyclobutane pyrimidine dimers. Proc Natl Acad Sci U S A 94:5255-60
Vink, A A; Yarosh, D B; Kripke, M L (1996) Chromophore for UV-induced immunosuppression: DNA. Photochem Photobiol 63:383-6
Vink, A A; Strickland, F M; Bucana, C et al. (1996) Localization of DNA damage and its role in altered antigen-presenting cell function in ultraviolet-irradiated mice. J Exp Med 183:1491-500
Nishigori, C; Yarosh, D B; Ullrich, S E et al. (1996) Evidence that DNA damage triggers interleukin 10 cytokine production in UV-irradiated murine keratinocytes. Proc Natl Acad Sci U S A 93:10354-9
Kripke, M L; Cox, P A; Bucana, C et al. (1996) Role of DNA damage in local suppression of contact hypersensitivity in mice by UV radiation. Exp Dermatol 5:173-80

Showing the most recent 10 out of 17 publications