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.
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.
|Boddupalli, Chandra Sekhar; Nair, Shiny; Gray, Simon M et al. (2016) ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells. J Clin Invest 126:3905-3916|
|Nair, Shiny; Branagan, Andrew R; Liu, Jun et al. (2016) Clonal Immunoglobulin against Lysolipids in the Origin of Myeloma. N Engl J Med 374:555-61|
|Dhodapkar, Madhav V (2016) MGUS to myeloma: a mysterious gammopathy of underexplored significance. Blood 128:2599-2606|
|Das, Rituparna; Strowig, Till; Verma, Rakesh et al. (2016) Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice. Nat Med 22:1351-1357|
|Dhodapkar, Madhav V; Dhodapkar, Kavita M (2015) Immune Modulation in Hematologic Malignancies. Semin Oncol 42:617-25|
|Das, Rituparna; Verma, Rakesh; Sznol, Mario et al. (2015) Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol 194:950-9|
|Sureshbabu, Angara; Syed, Mansoor A; Boddupalli, Chandra Sekhar et al. (2015) Conditional overexpression of TGFÎ²1 promotes pulmonary inflammation, apoptosis and mortality via TGFÎ²R2 in the developing mouse lung. Respir Res 16:4|
|Nair, Shiny; Boddupalli, Chandra Sekhar; Verma, Rakesh et al. (2015) Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation. Blood 125:1256-71|
|Zhao, S; Choi, M; Heuck, C et al. (2014) Serial exome analysis of disease progression in premalignant gammopathies. Leukemia 28:1548-52|
|Sehgal, Kartik; Ragheb, Ragy; Fahmy, Tarek M et al. (2014) Nanoparticle-mediated combinatorial targeting of multiple human dendritic cell (DC) subsets leads to enhanced T cell activation via IL-15-dependent DC crosstalk. J Immunol 193:2297-305|
Showing the most recent 10 out of 45 publications