5- Fluorouracil regulation of myeloid-derived suppressor cell differentiation in vitro and in vivo

• DOI: 10.4049/jimmunol.198.supp.205.5
• Publication Date: 2023-01-01T11:03:13Z
• Authors: John David Klement; Amy V Paschall; Natasha M Savage; Asha Nayak-Kapoor; Kebin Liu
• Keywords: Myeloid-derived Suppressor Cell

Abstract The chemotherapeutic agent 5-fluorouracil (5-FU) is the standard therapy for patients with advanced colorectal cancer (CRC). 5-FU not only targets tumor cells apoptosis but also induces in myeloid cells, leading to myelosuppression, which has long been thought as a side effect of therapy. Myeloid-derived suppressive (MDSCs) are heterogeneous population immature that exhibit potent activity inhibit T and NK cell function. Recent studies have found suppresses MDSCs mouse models. However, we observed still massively accumulate human CRC after multiple rounds We hypothesize subset resistant selectively eliminates sensitive MDSCs, enriching 5-FU-resistant MDSCs. To test this hypothesis, made use both vitro BM-derived MDSC (BM-MDSC) vivo significantly decreases CD11b+Gr1+ accumulation an orthotopic colon model. BM-MDSCs can be induced by cytokines, including GM-CSF, G-CSF, M-CSF IL-6, either alone or combination. Cytological analysis indicates various cytokines induce BM-MDSC differentially acquire morphological appearance subsets, macrophage- granulocyte-like cells. Interestingly, all these display resistance 5-FU-induced following exposure at doses high 10 μg/mL. Our data some subsets 5-FU, providing rationale explain enrichment successive treatments 5-FU.