Immunoregulatory Monocyte Subset Promotes Metastasis Associated With Therapeutic Intervention for Primary Tumor

Shibuya, Tomoki; Kamiyama, Asami; Sawada, Hirotaka; Kikuchi, Kenta; Maruyama, Mayu; Sawado, Rie; Ikeda, Naoki; Asano, Kenichi; Kurotaki, Daisuke; Tamura, Tomohide; Yoneda, Atsuko; Imada, Katsumi; Satoh, Takashi; Akira, Shizuo; Tanaka, Masato; Yotsumoto, Satoshi

doi:10.3389/fimmu.2021.663115

Cited by 21 publications

(18 citation statements)

References 54 publications

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“…1b). Lung tumor burdens were also found to be lower in IAV-infected mice, as demonstrated by reduced B16-luc-specific gene transcripts of premelanosome (Pmel) 34 and luciferase in the lung (Extended Data Fig. 2a) and reduced luciferin tumor signals in the lung area (Fig.…”

Section: Acute Iav Infection Induces Long-lasting Pulmonary Antitumor...mentioning

confidence: 92%

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Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs

et al. 2023

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Section: Acute Iav Infection Induces Long-lasting Pulmonary Antitumor...mentioning

confidence: 92%

“…injection of B16-luc cells expressing green fluorescent protein (GFP) 27,35 . By quantifying gene transcripts of premelanosome (Pmel), dopachrome tautomerase (Dct) 34 and luciferase as well as the numbers of CD45 -GFP + B16 cells, we showed comparable early tumor burdens in the lungs between PBS-treated and IAV-infected mice (Extended Data Fig. 2c,d).…”

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confidence: 85%

Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs

et al. 2023

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“…While the literature is controversial about the importance of MCP1 in obesity-induced inflammation ( 47 , 48 ), using the chemokine and PA treatment, we identified that male monocytes specifically have a more robust trafficking response in vitro. Sex differences in migration could be attributed to monocytes being heterogenous in nature with respect to the various chemokine and cytokine receptors where some are involved in tissue damage, while others promote tissue repair ( 49 – 51 ). MCSF facilitates tissue repair by recruiting monocytes to inflammation sites through CCR2 receptor activation and induction of CCL2/MCP1 production ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Monocyte Trafficking and Polarization Contribute to Sex Differences in Meta-Inflammation

et al. 2022

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Obesity is associated with systemic inflammation and immune cell recruitment to metabolic tissues. Sex differences have been observed where male mice challenged with high fat diet (HFD) exhibit greater adipose tissue inflammation than females demonstrating a role for sex hormones in differential inflammatory responses. Circulating monocytes that respond to dietary lipids and chemokines and produce cytokines are the primary source of recruited adipose tissue macrophages (ATMs). In this study, we investigated sexual dimorphism in biological pathways in HFD-fed ATMs from male and female mice by RNA-seq. We also conducted chemotaxis assays to investigate sex differences in the migration of monocytes isolated from bone marrow from male and female mice toward a dietary saturated lipid — palmitate (PA), and a chemokine — monocyte chemoattractant protein 1 (MCP1), factors known to stimulate myeloid cells in obesity. ATM RNA-Seq demonstrated sex differences of both metabolic and inflammatory activation, including pathways for chemokine signaling and leukocyte trans-endothelial migration. In vivo monocyte transfer studies demonstrated that male monocytes traffic to female adipose tissue to generate ATMs more readily. In chemotaxis assays, lean male monocytes migrated in greater numbers than females toward PA and MCP1. With short-term HFD, male and female monocytes migrated similarly, but in chronic HFD, male monocytes showed greater migration than females upon PA and MCP1 stimulation. Studies with monocytes from toll-like receptor 4 knockout mice (Tlr4-/-) demonstrated that both males and females showed decreased migration than WT in response to PA and MCP1 implying a role for TLR4 in monocyte influx in response to meta-inflammation. Overall, these data demonstrate the role of sexual dimorphism in monocyte recruitment and response to metabolic stimuli that may influence meta-inflammation in obesity.

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“…There were notable increases in the numbers of monocytes (Ly6C + and Ly6C – ) and neutrophils in the metastasis models. A recent study showed that the number of Ym1 + /Ly6C hi monocytes was increased in the peripheral blood of mice with early stages of lung metastasis, suggesting that the proportion of monocytes can be used as a biomarker of metastasis ( 22 ). Another study reported that injection of LLC1 cells to mice with Ifnar1 promoted the development of lung metastasis together with the accumulation of neutrophils in the lung, indicating the involvement of neutrophils in metastasis ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Picturing of the Lung Tumor Cellular Composition by Multispectral Flow Cytometry

et al. 2022

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The lung tumor microenvironment plays a critical role in the tumorigenesis and metastasis of lung cancer, resulting from the crosstalk between cancer cells and microenvironmental cells. Therefore, comprehensive identification and characterization of cell populations in the complex lung structure is crucial for development of novel targeted anti-cancer therapies. Here, a hierarchical clustering approach with multispectral flow cytometry was established to delineate the cellular landscape of murine lungs under steady-state and cancer conditions. Fluorochromes were used multiple times to be able to measure 24 cell surface markers with only 13 detectors, yielding a broad picture for whole-lung phenotyping. Primary and metastatic murine lung tumor models were included to detect major cell populations in the lung, and to identify alterations to the distribution patterns in these models. In the primary tumor models, major altered populations included CD324+ epithelial cells, alveolar macrophages, dendritic cells, and blood and lymph endothelial cells. The number of fibroblasts, vascular smooth muscle cells, monocytes (Ly6C+ and Ly6C–) and neutrophils were elevated in metastatic models of lung cancer. Thus, the proposed clustering approach is a promising method to resolve cell populations from complex organs in detail even with basic flow cytometers.

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Immunoregulatory Monocyte Subset Promotes Metastasis Associated With Therapeutic Intervention for Primary Tumor

Cited by 21 publications

References 54 publications

Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs

Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs

Monocyte Trafficking and Polarization Contribute to Sex Differences in Meta-Inflammation

Picturing of the Lung Tumor Cellular Composition by Multispectral Flow Cytometry

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