NSC243928 Treatment Induces Anti-Tumor Immune Response in Mouse Mammary Tumor Models

SIMPLE SUMMARY: This study used two different syngeneic mouse mammary tumor models to determine the effect of a small molecule NSC243928 on intra-tumoral immune cells. We observed that NSC243928 treatment reduced the tumor burden in vivo and altered the wide range of immune cell infiltration in both models. These results pave the path for further study of the role of NSC243928 in immuno-oncology drug development for triple-negative breast cancer. ABSTRACT: NSC243928 induces cell death in triple-negative breast cancer cells in a LY6K-dependent manner. NSC243928 has been reported as an anti-cancer agent in the NCI small molecule library. The molecular mechanism of NSC243928 as an anti-cancer agent in the treatment of tumor growth in the syngeneic mouse model has not been established. With the success of immunotherapies, novel anti-cancer drugs that may elicit an anti-tumor immune response are of high interest in the development of novel drugs to treat solid cancer. Thus, we focused on studying whether NSC243928 may elicit an anti-tumor immune response in the in vivo mammary tumor models of 4T1 and E0771. We observed that NSC243928 induced immunogenic cell death in 4T1 and E0771 cells. Furthermore, NSC243928 mounted an anti-tumor immune response by increasing immune cells such as patrolling monocytes, NKT cells, B1 cells, and decreasing PMN MDSCs in vivo. Further studies are required to understand the exact mechanism of NSC243928 action in inducing an anti-tumor immune response in vivo, which can be used to determine a molecular signature associated with NSC243928 efficacy. NSC243928 may be a good target for future immuno-oncology drug development for breast cancer.