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Poster Presentation
Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells
  1. Kibem Kim1,
  2. Andrew Skora2,
  3. Zhaobo Li2,
  4. Ada Tam3,
  5. Luis Diaz2,
  6. Nickolas Papadopolous2,
  7. Lee Blosser3,
  8. Kenneth Kinzler2,
  9. Bert Vogelstein2 and
  10. Shibin Zhou2
  1. Aff1 grid.21107.350000000121719311Medical Scientist Training Program, Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer CenterThe Johns Hopkins University School of Medicine Baltimore MD USA
  2. Aff2 grid.21107.350000000121719311Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer CenterThe Johns Hopkins University School of Medicine Baltimore MD USA
  3. Aff3 grid.21107.350000000121719311Department of Oncology, Sidney Kimmel Comprehensive Cancer CenterThe Johns Hopkins University School of Medicine Baltimore MD USA

https://doi.org/10.1186/2051-1426-2-S3-P267

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    Meeting abstracts

    Recent clinical trials have shown highly promising responses in a subset of patients treated with immune checkpoint inhibitory anti-programmed cell death-1, anti-programmed cell death ligand-1 (PD-1), and anti-cytotoxic T-lymphocyte-associated antigen-4 antibodies (CTLA-4) [1–4]. However, immunotherapy against poorly immunogenic cancers remains a challenge. Large, modestly immunogenic CT26 tumors or poorly immunogenic metastatic 4T1 tumors in mice were unresponsive to anti-PD-1 and anti-CTLA-4 treatments. Co-treatment with DNA methyltransferase and HDAC inhibitors, and checkpoint inhibitors markedly improved treatment outcomes, curing more than 80% of the tumor-bearing mice. Functional studies revealed that the primary targets of the epigenetic modulators were myeloid-derived suppressor cells (MDSCs). In addition, reduction of MDSCs using antibodies directed against them or a PI3K inhibitor that reduced circulating MDSCs had similar antitumor effects to those observed with the epigenetic modulators. Our results show that elevated myeloid-derived suppressor cells (MDSCs) are responsible for the resistance to checkpoint inhibitors and that elimination of MDSCs can lead to cures of experimental, metastatic tumors.

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