Malignant melanoma (MM) is one of the most invasive human cancers with its relative resistance to conventional chemotherapy and radiotherapy;only a small percentage of patients demonstrated durable responses to immunotherapy. Thus, a personalized strategy is urgently needed to develop assays which may guide the individual patient in the selection of appropriate therapy. Discovery of predictive biomarkers for immunotherapy response is an important strategy to attain this objective, which is stated in "Provocative Questions" for this RFA. MicroRNAs (miRNA) are small non-coding RNAs which regulate gene expression. Altered miRNA expression in tumor cells are found in variety types of cancer and contribute to therapy resistance in some cancer. We recently found that miRNAs are involved in immune cell development and function, and that cell-free serum from MM patients contains MM-specific miRNAs, which may serve as biomarkers for MM early diagnosis and prognosis. This application is designed to test the hypothesis that different miRNA expression profiles can be detected, either in MM tumor or in therapeutic targeting T cells, between patients who are responsive and who are resistant to immunotherapy. These differences could be reflected in the serum, which can potentially serve as convenient, noninvasive biomarkers for prediction of response to immunotherapy. We will begin by identifying the tumor-specific (Aim 1) and T cell-specific (Aim 2) miRNA expression profiles between therapy-responsive and therapy-resistant patients using TaqMan TR-PCR arrays;then will define serum specific miRNAs. The results from the proposed pioneering studies may enable us to predict MM patients who will respond to immunotherapy, using tissue/serum miRNAs as biomarkers, and may also facilitate the development of new intervention strategies for increasing immunotherapy for MM.

Public Health Relevance

Malignant melanoma (MM) is one of the most invasive human cancers with high potential for metastasis. The management of MM has been challenging due to its relative resistance to conventional therapy and immunotherapy. Discovery of predictive biomarkers for immunotherapy response is an important strategy to guide the individual patient in the selection of appropriate therapy, which is stated in Provocative Questions of this RFA. MicroRNAs (miRNA), small non-coding RNAs which regulate gene expressions, are involved in cancer development. This application is designed to identify specific miRNAs in MM tumor, therapeutic targeting T cells, and the serum as biomarkers for prediction of response to immunotherapy. The results from the proposed studies may enable us to predict MM patients who will respond to immunotherapy, and may also facilitate the development of new intervention strategies for increasing immunotherapy for MM.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA170535-02
Application #
8549182
Study Section
Special Emphasis Panel (ZCA1-SRLB-D (M1))
Program Officer
Thurin, Magdalena
Project Start
2012-09-21
Project End
2014-08-31
Budget Start
2013-09-13
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$179,712
Indirect Cost
$57,042
Name
Henry Ford Health System
Department
Type
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Shi, Yu-Ling; Weiland, Matthew; Lim, Henry W et al. (2014) Serum miRNA expression profiles change in autoimmune vitiligo in mice. Exp Dermatol 23:140-2