Date of Graduation
5-2015
Document Type
Thesis (MS)
Program Affiliation
Biochemistry and Molecular Biology
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Richard Eric Davis, M.D.
Committee Member
Sattva Neelapu, M.D.
Committee Member
Scott Kopetz, M.D., Ph.D.
Committee Member
Jorge Romaguera, M.D.
Committee Member
Rebert Bast, Jr., M.D.
Abstract
There are important but ill-defined interactions between benign immune cell subsets and neoplastic B cells within follicular lymphoma (FL). Using the novel technique of correlation matrix analysis (CMA) of publicly available FL whole-tumor gene expression profiling (GEP) data, we have identified signatures of immune cell subsets. Overall survival correlated most highly with a model using signatures of macrophages, T cells, and stroma, which was able to add significantly to existing clinical prognostic tools. From our own data of a cohort of 43 FL tumors sorted into B-cell and non-B cell (NB) fractions for GEP, CMA of the tumor infiltrating NB fraction revealed additional immune cell subset signatures, including T follicular helper (TFH) cells. Comparison of gene signatures between FL and tonsils (n=24) suggested that TFH cells and macrophages are qualitatively distinct in FL from normal tissue. “Cross-correlation”, between FL NB fraction signatures and individual B fraction genes, suggests that TFH cells promote proliferation, germinal center stage differentiation, B-cell receptor signaling, and induction of CCL17 and CCL22 by tumor B cells. This novel analytical approach may be broadly applicable to define gene signatures of rare immune cell subsets in the tumor microenvironment, determine their prognostic impact, discover novel therapeutic targets, and identify patients likely to benefit from therapies targeting tumor-stroma interactions.
Keywords
Follicular lymphoma, lymphoma, correlation matrix, gene signatures, gene expression profiling, immune cells, gene signatures, B-cell lymphoma
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Diagnosis Commons, Genetic Phenomena Commons, Genetic Processes Commons, Hematology Commons, Investigative Techniques Commons, Medical Genetics Commons, Oncology Commons, Other Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons, Therapeutics Commons