Defining the critical cellular elements of the stroma that support B lymphoma progression at lymphoid and non- lymphoid sites is of great therapeutic potential, yet remains an understudied area of research. The presence of follicular dendritic cells (FDCs) is a hallmark of lymphoid neogenesis in tumors, including B lymphomas. However, the functional importance of the these cells has not been addressed. Herein we will utilize patient- derived follicular lymphoma samples, two murine models of B-NHL, FDC-deficient mice and antibody blocking experiments to determine the contribution of FDC support to B lymphoma formation, progression and dissemination. Lymphoma cells present in lymphoid and neo-lymphoid microenvironments will be further characterized to identify engaged signaling pathways and gene expression signatures to establish profiles of the lymphoma cells, and provide the framework for future studies to investigate the significance and therapeutic potential of particular signaling nodes and microenvironmental factors.

Public Health Relevance

B cell differentiation and survival is dependent upon the local microenvironment. Manipulating B cell-stroma interactions is an underappreciated area of investigation with striking potential for therapeutic intervention in B cell malignancies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA195431-02
Application #
9254489
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (J1))
Program Officer
Jhappan, Chamelli
Project Start
2016-04-05
Project End
2018-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
2
Fiscal Year
2017
Total Cost
$190,856
Indirect Cost
$92,981
Name
Sanford Burnham Prebys Medical Discovery Institute
Department
Type
Research Institutes
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Ramezani-Rad, Parham; Rickert, Robert C (2017) Murine models of germinal center derived-lymphomas. Curr Opin Immunol 45:31-36