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NSC243928 Treatment Induces Anti-Tumor Immune Response in Mouse Mammary Tumor Models
Benson Chellakkan Selvanesan1,2, Alvaro de Mingo Pulido3, Sheelu Varghese1,2
1Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
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.
Insights
NSC243928 triggers cancer cell death and activates the immune system in breast cancer models. This compound shows potential for developing new immuno-oncology drugs for breast cancer treatment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) remains a challenge due to limited treatment options.
- Novel anti-cancer agents that can elicit an anti-tumor immune response are of significant interest.
- The anti-cancer mechanism of NSC243928, identified in the NCI library, is not fully understood.
Purpose of the Study:
- To investigate the anti-tumor immune response induced by NSC243928 in vivo.
- To explore the potential of NSC243928 as an immuno-oncology drug for breast cancer.
Main Methods:
- Utilized 4T1 and E0771 syngeneic mouse models of breast cancer.
- Assessed NSC243928's effect on cancer cell death and immune cell populations in vivo.
- Analyzed changes in immune cell subsets, including monocytes, NKT cells, B1 cells, and PMN-MDSCs.
Main Results:
- NSC243928 induced immunogenic cell death in 4T1 and E0771 breast cancer cells.
- In vivo, NSC243928 modulated the immune microenvironment by increasing beneficial immune cells and decreasing suppressive cells.
- Observed increases in patrolling monocytes, NKT cells, and B1 cells, alongside a decrease in polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs).
Conclusions:
- NSC243928 demonstrates potential as an immuno-oncology agent for breast cancer.
- The compound elicits an anti-tumor immune response, suggesting a role in enhancing cancer immunotherapy.
- Further research is needed to elucidate the precise molecular mechanisms and identify biomarkers for NSC243928 efficacy.
