Research Overview
Our research is centered on mechanisms of pathogenesis responsible for skin cancer. There are well over 1 million skin cancers diagnosed in the United States each year. While most are easily treated some result in significant morbidity and in some cases death. This is particularly true with squamous cell carcinoma (SCC) in immune suppressed transplant patients. In order to define mechanisms responsible for aggressive SCC in transplant patients, we first set out to characterize the “molecular fingerprint” for SCC in immune competent patients define the immune microenvironment associated with human skin cancers. In our initial studies, we found that human SCC was defined by a gene set specifically associated with malignant hyperproliferation. Included among these were genes governing immune and inflammatory responses Through immunohistochemistry and immunofluorescence microscopy we found that effector T cells (CD8 ) and immature dendritic cells (CD1a ) were associated with SCC suggesting the potential for a local antitumor response. In other studies, we found that regulatory T cells (CD4 CD25 Foxp3 ) were present in the microenvironment associated with human basal cell carcinoma (BCC). We further showed that cytokine microenvironment associated with BCC favored a Th2 type response which might be tumor permissive. We are currently expanding our studies to compare SCC in immune competent patients vs. SCC in transplant patients. We hope to fully characterize, compare and contrast the microenvironments associated with tumors from both groups of patients. In addition we are currently working to ascertain the phenotype and measure the stimulatory capacity of dendritic cells from tumors and adjacent non-tumor bearing skin. We are also currently working to determine the numbers and measure the suppressive capacity of regulatory T cells from human skin cancers. Through our studies we hope to identify ways to generate for tumor specific immune based therapies. Selected Publications: 1. Kaporis, H, et al. Foxp3 T cells are associated with human basal cell carcinoma in a Th2 dominant microenvironment. J. Invest. Dermatol. Oct;127(10) 2391-8. 2. Guttman-Yasky,E., et al. Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis. J. All. Clin. Immunol. 2007 May;119(5):1210-7. 3. Haider, A, Peters, S.B., Kaporis, H. Genomic Analysis Defines a Cancer Specific Gene Expression Signature for Human Squamous Cell Carcinoma and Distinguishes Malignant Hyperproliferation from Benign Hyperplasia J Invest Dermatol. 2006 Apr;126(4):869-81 4. Carucci, JA. Cutaneous oncology in organ transplant recipients: meeting the challenge of squamous cell carcinoma. J Invest Dermatol. 2004 Nov;123(5):809-16. 5. Carucci, JA., Martinez, JC, Zeitouni, NC, Christensen, L, Coldiron, B., Zweibel, S., Otley, CC., In transit metastases from primary cutaneous squamous cell carcinoma in organ transplant recipients and non-immunosuppressed patients. Clinical characteristics, management and outcome in a series of 21 patients. Dermatol. Surg. 2004; 30(4 pt 2):651-5. 6. Carucci, JA, Ignatius, R, Wei, Y, Cypess, AM, Pope, M, Steinman, RM, Mojsov, S. CGRP decreases expression of HLA-DR and CD86 by dendritic cells and suppresses DC driven T cell responses. J. Immunol. 2000; 164(7): 3494-3499.
