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.
| Stroncek, David F; Butterfield, Lisa H; Cannarile, Michael A et al. (2017) Systematic evaluation of immune regulation and modulation. J Immunother Cancer 5:21 |
| Dhodapkar, Madhav V; Borrello, Ivan; Cohen, Adam D et al. (2017) Hematologic Malignancies: Plasma Cell Disorders. Am Soc Clin Oncol Educ Book 37:561-568 |
| Branagan, Andrew R; Duffy, Eamon; Albrecht, Randy A et al. (2017) Clinical and Serologic Responses After a Two-dose Series of High-dose Influenza Vaccine in Plasma Cell Disorders: A Prospective, Single-arm Trial. Clin Lymphoma Myeloma Leuk 17:296-304.e2 |
| Dhodapkar, Madhav V; Kumar, Vipin (2017) Type II NKT Cells and Their Emerging Role in Health and Disease. J Immunol 198:1015-1021 |
| 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 |
| 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 |
| Boddupalli, Chandra Sekhar; Bar, Noffar; Kadaveru, Krishna et al. (2016) Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells. JCI Insight 1:e88955 |
| 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 |
| Dhodapkar, Kavita; Dhodapkar, Madhav (2016) Harnessing shared antigens and T-cell receptors in cancer: Opportunities and challenges. Proc Natl Acad Sci U S A 113:7944-5 |
| Dhodapkar, Madhav V (2016) MGUS to myeloma: a mysterious gammopathy of underexplored significance. Blood 128:2599-2606 |
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