{"doi":"10.1101/2022.07.08.499173","title":"Glioma-derived CCL2 and CCL7 mediate migration of immune suppressive CCR2 <sup>+</sup> myeloid cells into the tumor microenvironment in a redundant manner","abstract":"Abstract Glioblastoma (GBM) is the most common and malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized in part by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive, hematopoietic cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a potent subset of myeloid cells, expressing monocytic (M)-MDSC markers, distinguished by dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate into the TME. This study evaluated the T cell suppressive function and migratory properties of CCR2 + /CX3CR1 + MDSCs. Bone marrow-derived CCR2 + /CX3CR1 + cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Recombinant and glioma-derived CCL2 and CCL7 induce the migration of CCR2 + /CX3CR1 + MDSCs with similar efficacy. KR158B-CCL2 and -CCL7 knockdown murine gliomas contain equivalent percentages of CCR2 + /CX3CR1 + MDSCs compared to KR158B gliomas. Combined neutralization of CCL2 and CCL7 completely blocks CCR2-expressing cell migration to KR158B cell conditioned media. High levels of CCL2 and CCL7 are also associated with negative prognostic outcomes in GBM patients. These data provide a more comprehensive understanding of the function of CCR2 + /CX3CR1 + MDSCs and the role of CCL2 and CCL7 in the recruitment of these immune suppressive cells and further support the significance of targeting this chemokine axis in GBM.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298309,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":987751,"name":"Christian Kreiger","orcid":null,"position":1,"is_corresponding":false},{"id":987752,"name":"Defang Luo","orcid":null,"position":2,"is_corresponding":false},{"id":816551,"name":"Guimei Tian","orcid":null,"position":3,"is_corresponding":false},{"id":987753,"name":"Julia S. Garcia","orcid":null,"position":4,"is_corresponding":false},{"id":877525,"name":"Loic P. Deleyrolle","orcid":"0000-0002-1129-744X","position":5,"is_corresponding":false},{"id":281442,"name":"Duane A. Mitchell","orcid":"0000-0001-6049-213X","position":6,"is_corresponding":false},{"id":354511,"name":"Jeffrey K. Harrison","orcid":"0000-0002-1080-5721","position":7,"is_corresponding":false},{"id":354509,"name":"Gregory P. Takacs","orcid":"0000-0001-8415-432X","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:31:36.269611Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}