The Tang laboratory is focused on elucidating the role of secretory IgM (sIgM) produced by normal or cancerous B cells in activating myeloid-derived suppressor cells (MDSCs) to suppress anti-tumor T cell function within tumor microenvironments. MDSCs exert potent immunosuppressive functions within tumor microenvironments to promote tumor growth. It is critical to investigate the factors that can upregulate the functions of MDSCs because such studies can potentially lead to new treatment strategies to suppress the functions of MDSCs and reactivate the body’s immune response to combat cancer. In the short term, we will identify and characterize the mechanisms by which sIgM activates the immunosuppressive functions of MDSCs and to investigate how to target sIgM to control MDSCs.

Identifying and characterizing the molecular mechanisms of how secretory IgM exerts immunosuppressive function via activating MDSCs in tumors. MDSCs exert potent immunosuppressive functions within tumor microenvironments to promote tumor growth. It is critical to investigate the factors that can upregulate the functions of MDSCs because such studies can potentially lead to new treatment strategies to suppress the functions of MDSCs and reactivate the body’s immune response to combat cancer.

My published data generated from several tumor mouse models strongly support that sIgM produced by normal and leukemic B cells has strong immunosuppressive functions in inducing the accumulation and upregulating the functions of MDSCs. To be able to translate my results into potential therapeutic strategies, I decided to target the synthesis of sIgM by deleting the function of spliced XBP-1 (XBP-1s), because the synthesis of sIgM is tightly regulated by RIDD, which is hyperactivated in B cells as a response to deficiency of XBP-1s. Indeed, specific deletion of the XBP-1 gene in leukemic B cells and pharmacological inhibition of XBP-1s in a B cell leukemia mouse model can lead to downregulated immunosuppressive functions of MDSCs, supporting the therapeutic potential of targeting XBP-1s in inhibiting MDSCs. These data prompt me to identify and characterize the mechanisms by which sIgM activates the immunosuppressive functions of MDSCs and to investigate how to target sIgM to control MDSCs.

My goals are summarized in the following specific aims:

  1. To increase knowledge of how antibodies can orchestrate an immunosuppressive microenvironment to support tumor growth
  2. To perform in-depth analysis of animal models to guide the development of immunotherapy modalities for the treatment of cancers
  3. To improve cancer patients’ survival by boosting the immune system in tumor microenvironment