Title |
Anti-tumor Immunity in Myeloma
|
Institution |
YALE UNIVERSITY, NEW HAVEN, CT
|
Principal Investigator |
DHODAPKAR, MADHAV
|
NCI Program Director |
Kevin Howcroft
|
Cancer Activity |
Immunology
|
Division |
DCB
|
Funded Amount |
$322,425
|
Project Dates |
03/08/2004 - 03/31/2017
|
Fiscal Year |
2012
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
|
Multiple Myeloma (100.0%)
|
Research Type |
Cancer Initiation: Alterations in Chromosomes
Systemic Therapies - Discovery and Development
|
Abstract |
DESCRIPTION (provided by applicant): Interactions between tumor cells and the microenvironment (TME) have a major impact on the biology of myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS). This application is a continuation of our prior work wherein we characterized several aspects of TME in MM. A theme from our prior work is that transition of MGUS to MM is associated with several changes in TME, with loss of anti-tumor immunity and progressive inflammation. Herein we will pursue the link between properties of tumor cells and changes in TME. Based on our preliminary studies, we posit that secretion of wnt inhibitors by tumor cells and the recruitment of myeloid cells play a major role in the altered balance of immunity and inflammation. In Aim 1, we will pursue the effect of wnt inhibitors on the regulation of host immune response. In Aim 2, we will further characterize the crosstalk between myeloid cells and myeloma in the regulation of genomic instability. These studies may provide several targets to restore the dysregulation of immunity versus inflammation and restrict genomic instability in this cancer.
PUBLIC HEALTH RELEVANCE: This work builds on our prior studies to better understand the changes in the properties of the tumor bed in myeloma. These studies may provide novel approaches to control tumor growth and achieve durable responses to therapy. |