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.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/41151 |
| Date | 01 October 2020 |
| Creators | Martel, André Bernard |
| Contributors | Auer, Rebecca |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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