Medicine and Health Sciences Commons^™

Protective Cd8 Memory T Cell Responses To Mouse Melanoma Are Generated In The Absence Of Cd4 T Cell Help, Anik L. Côté, Katelyn T. Byrne, Shannon M. Steinberg, Peisheng Zhang, Mary Jo Turk

Dartmouth Scholarship

Background: We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 T cell responses to melanoma/melanocyte antigens. We also showed that persistence of these CD8 T cells is supported, in an antigen-dependent fashion, by concurrent autoimmune melanocyte destruction. Herein we explore the requirement of CD4 T cell help in priming and maintaining this protective CD8 T cell response to melanoma.

Mechanisms Of Resistance To Raf Inhibitors In Melanoma., A E Aplin, Fred M Kaplan, Yongping Shao

Department of Cancer Biology Faculty Papers

The recent RAF inhibitor trial with PLX4032/RG7204 in late-stage mutant B-RAF melanoma patients has been lauded as a success story for personalized cancer therapy since short-term clinical responses were observed in the majority of patients. However, initial responses were followed by subsequent tumor re-growth, and a subset of patients showed intrinsic resistance. Bi-directional translational efforts are now essential to determine the mechanisms underlying acquired/secondary and intrinsic resistance to RAF inhibitors.

Genetic Determinants Of Uv-Susceptibility In Non-Melanoma Skin Cancer, Marleen M. Welsh, Margaret R. Karagas, Jacquelyn K. Kuriger, Andres Houseman, Steven K. Spencer, Ann E. Perry, Heather H. Nelson

Dartmouth Scholarship

A milieu of cytokines and signaling molecules are involved in the induction of UV-induced immune suppression and thus the etiology of non-melanoma skin cancer (NMSC). Targeting the UV-induced immunosuppression pathway, and using a large population based study of NMSC, we have investigated the risk associated with functional variants in 10 genes (IL10, IL4, IL4R, TNF, TNFR2, HTR2A, HRH2, IL12B, PTGS2, and HAL). The most prominent single genetic effect was observed for IL10. There was increasing risk for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with …

Tumor-Derived Interleukin-10 As A Prognostic Factor In Stage Iii Patients Undergoing Adjuvant Treatment With An Autologous Melanoma Cell Vaccine., Amit Mahipal, Mizue Terai, David Berd, Inna Chervoneva, Kashyap Patel, Michael Mastrangelo, Takami Sato

Department of Medical Oncology Faculty Papers

OBJECTIVES: Interleukin-10 (IL-10) downregulates T-cell-mediated immune responses. We studied the association between IL-10 production by freshly isolated melanoma cell suspensions in vitro and overall survival in patients undergoing adjuvant treatment with a vaccine prepared from the same autologous melanoma cells modified with a hapten, dinitrophenyl (DNP).

METHODS: Forty-four patients with cutaneous melanoma (29 stage III and 15 stage IV) were prospectively evaluated. Tumor cells were extracted from metastatic deposits for production of DNP-modified autologous melanoma cell vaccine. Small aliquots of the melanoma cell suspensions were separated prior to vaccine processing and cultured overnight for IL-10 production. Based on a blind …

Expression Of Microphthalmia Transcription Factor In Sentinel Lymph Nodes Of Patients With Melanoma, Minia Hellan, Michelle S. Gentile, Luay Ailabouni, George I. Salti

Department of Surgery Faculty Publications

Background: Sentinel lymph node biopsy is widely used in the management of melanoma patients. Multiple markers are used to stain sentinel lymph node tissue including S100, HMB-45 and melan A with different success. We investigated, for the first time, the use of Microphthalmia transcription factor (Mitf) staining in a larger series of sentinel lymph nodes. Mitf is a transcription factor essential for the development and survival of melanocytes. It has been introduced recently as a sensitive and specific marker for melanomas. Methods: Thirty patients with cutaneous melanoma were included in our study: twenty patients underwent sentinel lymph node biopsy; ten …

Autoimmune Melanocyte Destruction Is Required For Robust Cd8+ Memory T Cell Responses To Mouse Melanoma, Katelyn T. Byrne, Anik L. Côté, Peisheng Zhang, Shannon M. Steinberg, Yanxia Guo, Rameeza Allie, Weijun Zhang, Marc S. Ernstoff, Edward J. Usherwood, Mary Jo Turk

Dartmouth Scholarship

A link between autoimmunity and improved antitumor immunity has long been recognized, although the exact mechanistic relationship between these two phenomena remains unclear. In the present study we have found that vitiligo, the autoimmune destruction of melanocytes, generates self antigen required for mounting persistent and protective memory CD8⁺ T cell responses to melanoma. Vitiligo developed in approximately 60% of mice that were depleted of regulatory CD4⁺ T cells and then subjected to surgical excision of large established B16 melanomas. Mice with vitiligo generated 10-fold larger populations of CD8⁺ memory T cells specific for shared melanoma/melanocyte antigens. CD8 …

Genetic Factors In Metastatic Progression Of Cutaneous Melanoma: The Future Role Of Circulating Melanoma Cells In Prognosis And Management, A Ireland, M Millward, R Pearce, M Lee, Mel Ziman

Research outputs pre 2011

The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material …

Comparative Study Of Long-And Short-Pulsed Electric Fields For Treating Melanoma In An In Vivo Mouse Model, Xinhua Chen, Xinmei Chen, Karl H. Schoenbach, Shusen Zheng, R. James Swanson

Bioelectrics Publications

A mouse melanoma model was set up with green fluorescent protein (GFP) expression in vivo. With the same energy, long- (1 ms) and short- (300 ns) pulsed electric fields were delivered to two melanomas injected into the same mouse. The tumor growth and green fluorescence were followed up to compare the different treatment efficacy of long and short pulses. After two days post treatment, short pulse-treated tumors showed a significantly lower tumor volume compared with long pulse-treated tumors (n=8, p