Correlation Matrix Analysis Identifies Gene Signatures of Immune Cell Subsets and Their Interactions In Follicular Lymphoma

<p>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.<strong></strong></p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2015

Author dc:creator

• Westin, Jason R.

Contributors dc:contributor

• Richard Eric Davis, M.D.
• Sattva Neelapu, M.D.
• Scott Kopetz, M.D., Ph.D.

• Follicular lymphoma
• lymphoma
• correlation matrix
• gene signatures
• gene expression profiling
• immune cells
• B-cell lymphoma
• Biological Phenomena, Cell Phenomena, and Immunity
• Diagnosis
• Genetic Phenomena
• Genetic Processes
• Hematology
• Investigative Techniques
• Medical Genetics
• Medicine and Health Sciences
• Oncology
• Other Analytical, Diagnostic and Therapeutic Techniques and Equipment
• Therapeutics

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/585

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1627