Tissue-resident macrophages promote early dissemination of multiple myeloma via IL-6 and TNFα.

ABSTRACT: Multiple myeloma (MM) is a plasma cell malignancy characterized by the presence of multiple foci in the skeleton. These distinct tumor foci represent cycles of tumor growth and dissemination that seed new clusters and drive disease progression. By using an intratibial Vk*MYC murine myeloma model, we found that CD169+ radiation-resistant tissue-resident macrophages (MPs) were critical for early dissemination of myeloma and disease progression. Depletion of these MPs had no effect on tumor proliferation, but it did reduce egress of myeloma from bone marrow (BM) and its spread to other bones. Depletion of MPs as a single therapy and in combination with BM transplantation improved overall survival. Dissemination of myeloma was correlated with an increased inflammatory signature in BM MPs. It w

SUBMITTER: Akhmetzyanova I 

PROVIDER: S-EPMC8945576 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature