Targeting CD155 on Myeloid Derived Suppressor Cells to Prevent Postoperative Immunosuppression in Cancer Patients

Abstract

Surgery, although required to treat most solid cancers, can increase tumour seeding and metastases. We have previously shown that surgery-induced myeloid derived suppressor cells (Sx-MDSCs) play an important role in this process by directly suppressing NK cells. The Sx- MDSCs increase significantly immediately after surgery but the exact mechanism by which Sx-MDSCs suppress NK cells is still unknown. In this work, we have discovered that CD155 poliovirus receptor is significantly and specifically upregulated on Sx-MDSCs following surgical stress but is minimally expressed on other immune cells. We also demonstrate that blocking CD155 in vivo leads to an improved NK cell phenotype, measured by DNAM-1 and NKG2D, and increased NK cytotoxicity. Additionally, ex vivo CD155 blockade significantly decreases the suppressive effect of Sx-MDSCs in cancer patients. Expansion of CD155 on Sx- MDSCs could be responsible for the profound postoperative NK cell suppression, which makes it a very appealing perioperative target for immunotherapy.