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1460 Treatment with small molecule NSC243928 in mouse mammary tumor model induces change in tumor microenvironment associated with anti-tumor immune responses
  1. Benson Selvanesan1,
  2. Alvaro De Mingo Pulido2,
  3. Sheelu Varghese1,
  4. Daniel Hupalo1,
  5. Yuriy Gusev3,
  6. Sara Contente4,
  7. Matthew Wilkerson5,
  8. Clifton Dalgard6,
  9. Geeta Upadhyay5 and
  10. Geeta Upadhyay7
  1. 1Henry Jackson Foundation, Bethesda, MD, USA
  2. 2Moffit Cancer Center, Tampa, FL, USA
  3. 3Innovation Center for Biomedical Inform, Washington DC, DC, USA
  4. 4Pathology, Uniformed Services University, Bethesda, USA
  5. 5Uniformed Services University of Health, Bethesda, MD, USA
  6. 6Center for Military Precision Health, Bethesda, MD, USA
  7. 7Uniformed Services University of Health Sciences, Bethesda, MD, USA


Background Previously, we identified that 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 NCI small molecule library. The molecular mechanism of NSC243928 as an anti-cancer agent in the treatment on tumor growth in the syngeneic mice model is not established. With the success of immunotherapies, novel drugs which may elicit an anti-tumor immune response in addition to effecting cancer cell death are of high interest for developing novel drugs to treat solid cancer.

Methods We focused on studying if NSC243928 may elicit an anti-tumor immune response in the in vivo mammary tumor models of 4T1 and E0771.

Results We observed that treatment with NSC243928 induced in vivo tumor mass reductions. The bulk RNA seq analysis of tumor isograft samples showed that NSC243928 generates anti-tumor immune responses in both models. NSC243928 induced cell surface calreticulin expression, indicative of immunogenic cell death in both tumor cell lines at the micromolar concentrations. NSC243928 treatment led to reduced MDSCs in the peripheral blood and increased levels of intra-tumoral immune cells namely- patrolling monocytes and MHC II positive tumor associated macrophages in both mouse models. We observed that NSC243928 showed intra-tumoral immune response such as increased NKT cells, decreased PMN-MDSCs and increased B1 cells in the E0771 mouse model.

Conclusions Taken together we conclude that NSC243928 induces a superior immune response in the E0771 mouse mammary tumor model. Further studies are required to understand the link of NSC243928 associated anti-tumor immune response to determine the adequate molecular signature associated NSC243928 efficacy could be identified, which will be beneficial to future drug development.

Acknowledgements NIH, NCI, R01 CA227694.

DOD, USUHS, VPR-NFP-74-9824.

NIH, NCI, R21 CA256424.

Biomedical Instrumentation Center, USUHS.

The American Genome Center, USUHS.

National Cancer Institute, National Institute of Health.

Disclaimer The opinions expressed herein are those of the authors and are not necessarily representative of the official policy of the Uniformed Services University of the Health Sciences (USUHS), the Department of Defense (DOD), the United States Army/Navy/Air Force, or the U.S. Government or any other funding agencies herein.

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