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Tumor-associated macrophages, dendritic cells, and neutrophils: biological roles, crosstalk, and therapeutic relevance.

ABSTRACT: Tumor-associated myeloid cells constitute a series of plastic and heterogeneous cell populations within the tumor microenvironment (TME), and exhibit different phenotypes and functions in response to various microenvironmental signals. In light of promising preclinical data indicating that myeloid-based therapy can effectively suppress tumor growth, a series of novel immune-based therapies and approaches are currently undergoing clinical evaluation. A better understanding of the diversity and functional roles of different myeloid cell subtypes and of how they are associated with TME remodeling may help to improve cancer therapy. Herein, we focus on myeloid cells and discuss how tumor cells can simultaneously reprogram these cells through tumor-derived factors and metabolites. In addition, we discuss the interactions between myeloid cells and other cells in the TME that have the potential to directly or indirectly regulate tumor initiation, invasion, or angiogenesis. We further discuss the current and future potential applications of myeloid cells in the development of focused therapeutic strategies in cancer treatment.

SUBMITTER: Shen M

PROVIDER: S-EPMC10388790 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Tumor-associated macrophages, dendritic cells, and neutrophils: biological roles, crosstalk, and therapeutic relevance.

Shen Mingyi M Du Yanhua Y Ye Youqiong Y

Medical review (2021) 20211201 2

Tumor-associated myeloid cells constitute a series of plastic and heterogeneous cell populations within the tumor microenvironment (TME), and exhibit different phenotypes and functions in response to various microenvironmental signals. In light of promising preclinical data indicating that myeloid-based therapy can effectively suppress tumor growth, a series of novel immune-based therapies and approaches are currently undergoing clinical evaluation. A better understanding of the diversity and fu ...[more]

PMID: 37724296

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Project description:ObjectiveTo evaluate the role of immune cells and their effector cytokines in the pathogenesis and progression of knee osteoarthritis (OA) in matched OA synovial fluid (SF) and synovial tissue samples.MethodsCells from matched samples of synovial tissue and SF acquired from individuals undergoing total knee replacement for OA (n = 39) were characterized for immune cell-associated surface markers and intracellular cytokine expression using polychromatic flow cytometry. Additional individuals with radiographic knee OA (Kellgren/Lawrence severity grades ≥1) who had available etarfolatide (inflammatory cell) imaging (n = 26) or baseline and 3-year data on progression of radiographic knee OA (n = 85) were also assessed. SF cytokine concentrations in all cohorts were evaluated for associations with synovial tissue and SF cell phenotypes and severity of radiographic knee OA.ResultsMacrophages (predominant in the synovial tissue, 53% of total cells) and neutrophils (predominant in the SF, 26% of total cells) were the major immune cell populations identified in the OA knee joints, exhibiting expression of or association with transforming growth factor β1 (TGFβ1) and elastase, respectively, in the SF. Expression levels of TGFβ1 and elastase were significantly associated with severity of radiographic knee OA. Baseline SF concentrations of TGFβ1 and elastase along with radiographic knee OA severity scores were predictive of knee OA progression, with areas under the receiver operating characteristic curves of 0.810 (for TGFβ1), 0.806 (for elastase), and 0.846 (for both TGFβ1 and elastase combined), with greater stability of prediction when both markers were utilized.ConclusionOur findings demonstrate the hitherto underappreciated role of neutrophils in the sterile inflammatory process and progression of OA. Two soluble mediators, SF elastase and TGFβ1, are strong predictors of knee OA progression, reflecting a synergistic role of neutrophil and macrophage populations in the pathogenesis and worsening of OA that could potentially be utilized to identify patients who may have a greater risk of more rapid disease progression.

Dataset Information

Tumor-associated macrophages, dendritic cells, and neutrophils: biological roles, crosstalk, and therapeutic relevance.

Publications

Tumor-associated macrophages, dendritic cells, and neutrophils: biological roles, crosstalk, and therapeutic relevance.

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