Resident stroma recruits myeloid-derived suppressor cells via CCL2/CCR2 axis in oral squamous cell carcinoma

ABSTRACT: In the tumour microenvironment (TME), stroma components play a vital role in tumour development. Myeloid-derived suppressor cells (MDSC) recruited by tumour cells in TME support tumour development. However, the influence of stroma on MDSC is unclear. Here we aimed to unveil the roles of stroma in the recruitment of MDSC in oral squamous cell carcinoma (OSCC). We created xenograft OSCC models on GFP+ bone marrow transplanted nude mice. We co-xenografted human OSCC cells line (HSC-2) with three different types of stromal cells, including human dermal fibroblasts (HDF) or patient-derived stromal cells (PDS1 and PDS2) isolated from two OSCC patients, or without stromal cells. Tumour/stroma co-xenograft models recruited significantly higher numbers of GFP+ bone marrow (BM) cells than the tumour cells alone xenografted group. However, only patient-derived stroma xenograft (PDSX) models promoted GR1/CD11b/Arg1 triple-positive MDSC, which was the main population influenced by stromal character and depended on the stroma secreted CCL2. In vitro inhibition of CCL2 synthesis in PDS cocultures also resulted in significantly decreased migration of BM cells than in HDF coculture and HSC-2 alone culture. Moreover, CCR2+ MDSC infiltrated considerably higher in PDSX models. Taken together, we demonstrated that stromal cells are responsible for MDSC recruitment and stroma secreted CCL2 play an essential role in MDSC recruitment in OSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164374 | GEO | 2021/08/18

REPOSITORIES: GEO