{"doi":"10.3389/fonc.2021.669066","title":"The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging","abstract":"An increased accumulation of immune-dysfunction-associated CD4 + Foxp3 + regulatory T cells (T regs ) is observed in aging oral mucosa during infection. Here we studied the function of T regs during oral cancer development in aging mucosa. First, we found heightened proportions of T regs and myeloid-derived suppressor cells (MDSC) accumulating in mouse and human oral squamous cell carcinoma (OSCC) tissues. Using the mouse 4-Nitroquinoline 1-oxide(4-NQO) oral carcinogenesis model, we found that tongues of aged mice displayed increased propensity for epithelial cell dysplasia, hyperplasia, and accelerated OSCC development, which coincided with significantly increased abundance of IL-1β, T regs , and MDSC in tongues. Partial depletion of T regs reduced tumor burden. Moreover, fungal abundance and dectin-1 signaling were elevated in aged mice suggesting a potential role for dectin-1 in modulating immune environment and tumor development. Confirming this tenet, dectin-1 deficient mice showed diminished IL-1β, reduced infiltration of T regs and MDSC in the tongues, as well as slower progression and reduced severity of tumor burden. Taken together, these data identify an important role of dectin-1 signaling in establishing the intra-tumoral immunosuppressive milieu and promoting OSCC tumorigenesis in the context of aging.","journal":"Frontiers in Oncology","year":2021,"id":171603,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":339586,"name":"Sangeetha Jayaraman","orcid":"0000-0002-9300-8890","position":1,"is_corresponding":false},{"id":707041,"name":"Cheriese Quigley","orcid":null,"position":2,"is_corresponding":false},{"id":339587,"name":"Prerna Mamileti","orcid":"0000-0002-9497-3211","position":3,"is_corresponding":false},{"id":707042,"name":"Mahmoud Ghannoum","orcid":null,"position":4,"is_corresponding":false},{"id":339588,"name":"Aaron Weinberg","orcid":"0000-0002-9960-7181","position":5,"is_corresponding":false},{"id":706387,"name":"Jason E. Thuener","orcid":"0000-0002-5035-4611","position":6,"is_corresponding":false},{"id":425789,"name":"Quintin Pan","orcid":"0000-0001-6952-3529","position":7,"is_corresponding":false},{"id":339589,"name":"Pushpa Pandiyan","orcid":"0000-0003-3688-0794","position":8,"is_corresponding":false},{"id":339584,"name":"Natarajan Bhaskaran","orcid":"0000-0003-2823-5170","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:46:33.067299Z","pmid":"33968777","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":[]}