Anti-tumor Immunity in Myeloma

描述（由申请人提供）：肿瘤细胞与微环境（TME）之间的相互作用对骨髓瘤（MM）及其意义不明的前体单克隆丙种球蛋白病（MGUS）的生物学具有重大影响。本申请是我们先前工作的延续，其中我们表征了MM中TME的几个方面。我们先前工作的主题是MGUS向MM的转变与TME的几个变化相关，具有抗肿瘤免疫力的丧失和进行性炎症。在此，我们将探讨肿瘤细胞的性质和TME变化之间的联系。基于我们的初步研究，我们认为肿瘤细胞分泌wnt抑制剂和骨髓细胞的募集在免疫和炎症平衡的改变中起主要作用。在目标1中，我们将追求wnt抑制剂对宿主免疫应答的调节的作用。在目标2中，我们将进一步表征骨髓细胞和骨髓瘤在基因组不稳定性调节中的串扰。这些研究可能提供几个目标，以恢复免疫与炎症的失调，并限制这种癌症的基因组不稳定性。

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.