TUMOR-INFILTRATING NOCICEPTOR NEURONS PROMOTE IMMUNOSUPPRESSION [MDSC]
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PROVIDER: PRJNA1282117 | ENA |
REPOSITORIES: ENA
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Project description:TUMOR-INFILTRATING NOCICEPTOR NEURONS PROMOTE IMMUNOSUPPRESSION
| PRJNA1279977 | ENA
Project description:Nociceptor neurons impact tumor immunity. Removing nociceptor neurons reduced myeloid-derived suppressor cell (MDSCs) tumor infiltration in mouse models of head and neck carcinoma and melanoma. Carcinoma-released small extracellular vesicles (sEVs) attract nociceptive nerves to tumors. sEV-deficient tumors fail to develop in mice lacking nociceptor neurons. Exposure of dorsal root ganglia (DRG) neurons to cancer sEVs elevated expression of Substance P, IL-6 and injury-related neuronal markers while treatment with cancer sEVs and cytotoxic CD8 T-cells induced an immunosuppressive state (increased exhaustion ligands and cytokines). Cancer patient sEVs enhanced DRG responses to capsaicin, indicating increased nociceptor sensitivity. Conditioned media from DRG and cancer cell co-cultures promoted expression of MDSC markers in primary bone marrow cells while DRG conditioned media together with cancer sEVs induced checkpoint expression on T-cells. Our findings indicate that nociceptor neurons facilitate CD8+ T cell exhaustion and enhance MDSC infiltration. Targeting nociceptor-released IL-6 emerges as a novel strategy to disrupt harmful neuro-immune interactions in cancer and enhance anti-tumor immunity.
2025-08-07 | GSE300787 | GEO
Project description:Nociceptor neurons impact tumor immunity. Removing nociceptor neurons reduced myeloid-derived suppressor cell (MDSCs) tumor infiltration in mouse models of head and neck carcinoma and melanoma. Carcinoma-released small extracellular vesicles (sEVs) attract nociceptive nerves to tumors. sEV-deficient tumors fail to develop in mice lacking nociceptor neurons. Exposure of dorsal root ganglia (DRG) neurons to cancer sEVs elevated expression of Substance P, IL-6 and injury-related neuronal markers while treatment with cancer sEVs and cytotoxic CD8 T-cells induced an immunosuppressive state (increased exhaustion ligands and cytokines). Cancer patient sEVs enhanced DRG responses to capsaicin, indicating increased nociceptor sensitivity. Conditioned media from DRG and cancer cell co-cultures promoted expression of MDSC markers in primary bone marrow cells while DRG conditioned media together with cancer sEVs induced checkpoint expression on T-cells. Our findings indicate that nociceptor neurons facilitate CD8+ T cell exhaustion and enhance MDSC infiltration. Targeting nociceptor-released IL-6 emerges as a novel strategy to disrupt harmful neuro-immune interactions in cancer and enhance anti-tumor immunity.
2025-08-07 | GSE300254 | GEO
Project description:Nociceptor neurons impact tumor immunity. Removing nociceptor neurons reduced myeloid-derived suppressor cell (MDSCs) tumor infiltration in mouse models of head and neck carcinoma and melanoma. Carcinoma-released small extracellular vesicles (sEVs) attract nociceptive nerves to tumors. sEV-deficient tumors fail to develop in mice lacking nociceptor neurons. Exposure of dorsal root ganglia (DRG) neurons to cancer sEVs elevated expression of Substance P, IL-6 and injury-related neuronal markers while treatment with cancer sEVs and cytotoxic CD8 T-cells induced an immunosuppressive state (increased exhaustion ligands and cytokines). Cancer patient sEVs enhanced DRG responses to capsaicin, indicating increased nociceptor sensitivity. Conditioned media from DRG and cancer cell co-cultures promoted expression of MDSC markers in primary bone marrow cells while DRG conditioned media together with cancer sEVs induced checkpoint expression on T-cells. Our findings indicate that nociceptor neurons facilitate CD8+ T cell exhaustion and enhance MDSC infiltration. Targeting nociceptor-released IL-6 emerges as a novel strategy to disrupt harmful neuro-immune interactions in cancer and enhance anti-tumor immunity.
| S-EPMC11382997 | biostudies-literature
Project description:Chronic inflammation and immunosuppressive microenvironment promote prostate cancer (PCa) metastasis and diminish the responses to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation induced IKKb activation to shape immunosuppressive tumor microenvironment (TME). Prostate-specific deletion of Arid1a cooperates with Pten loss to produce a metastasis-prone tumors. We identify that polymorphonuclear myeloid-derived suppressor cells (MDSCs) as the major infiltrating immune cell type to cause immune evasion, and neutralization of MDSCs restricts metastasis of Arid1a deficient tumors. Mechanistically, inflammation cues activate IKKβ to phosphorylate ARID1A, leading to its degradation via b-TRCP. ARID1A downregulation in turn silences the enhancer of A20 deubiquitinase, a critical negative regulator of NF-kB signaling, and thereby unleashing CXCR2 ligands-mediated MDSC chemotaxis. Importantly, our results support the therapeutic strategy of anti-NF-kB or CXCR2 combined with ICB for advanced PCa. Together, our findings highlight a critical role of ARID1A in MDSCs recruitment and demonstrate IKKb/ARID1A/NF-kB feedback axis integrating inflammation and the immunosuppression to drive PCa metastasis.
2022-11-07 | GSE197687 | GEO
Project description:Chronic inflammation and immunosuppressive microenvironment promote prostate cancer (PCa) metastasis and diminish the responses to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation induced IKKb activation to shape immunosuppressive tumor microenvironment (TME). Prostate-specific deletion of Arid1a cooperates with Pten loss to produce a metastasis-prone tumors. We identify that polymorphonuclear myeloid-derived suppressor cells (MDSCs) as the major infiltrating immune cell type to cause immune evasion, and neutralization of MDSCs restricts metastasis of Arid1a deficient tumors. Mechanistically, inflammation cues activate IKKβ to phosphorylate ARID1A, leading to its degradation via b-TRCP. ARID1A downregulation in turn silences the enhancer of A20 deubiquitinase, a critical negative regulator of NF-kB signaling, and thereby unleashing CXCR2 ligands-mediated MDSC chemotaxis. Importantly, our results support the therapeutic strategy of anti-NF-kB or CXCR2 combined with ICB for advanced PCa. Together, our findings highlight a critical role of ARID1A in MDSCs recruitment and demonstrate IKKb/ARID1A/NF-kB feedback axis integrating inflammation and the immunosuppression to drive PCa metastasis.
2022-11-07 | GSE197686 | GEO
Project description:Chronic inflammation and immunosuppressive microenvironment promote prostate cancer (PCa) metastasis and diminish the responses to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation induced IKKb activation to shape immunosuppressive tumor microenvironment (TME). Prostate-specific deletion of Arid1a cooperates with Pten loss to produce a metastasis-prone tumors. We identify that polymorphonuclear myeloid-derived suppressor cells (MDSCs) as the major infiltrating immune cell type to cause immune evasion, and neutralization of MDSCs restricts metastasis of Arid1a deficient tumors. Mechanistically, inflammation cues activate IKKβ to phosphorylate ARID1A, leading to its degradation via b-TRCP. ARID1A downregulation in turn silences the enhancer of A20 deubiquitinase, a critical negative regulator of NF-kB signaling, and thereby unleashing CXCR2 ligands-mediated MDSC chemotaxis. Importantly, our results support the therapeutic strategy of anti-NF-kB or CXCR2 combined with ICB for advanced PCa. Together, our findings highlight a critical role of ARID1A in MDSCs recruitment and demonstrate IKKb/ARID1A/NF-kB feedback axis integrating inflammation and the immunosuppression to drive PCa metastasis.
2022-11-07 | GSE197749 | GEO
Project description:Chronic inflammation and immunosuppressive microenvironment promote prostate cancer (PCa) metastasis and diminish the responses to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation induced IKKb activation to shape immunosuppressive tumor microenvironment (TME). Prostate-specific deletion of Arid1a cooperates with Pten loss to produce a metastasis-prone tumors. We identify that polymorphonuclear myeloid-derived suppressor cells (MDSCs) as the major infiltrating immune cell type to cause immune evasion, and neutralization of MDSCs restricts metastasis of Arid1a deficient tumors. Mechanistically, inflammation cues activate IKKβ to phosphorylate ARID1A, leading to its degradation via b-TRCP. ARID1A downregulation in turn silences the enhancer of A20 deubiquitinase, a critical negative regulator of NF-kB signaling, and thereby unleashing CXCR2 ligands-mediated MDSC chemotaxis. Importantly, our results support the therapeutic strategy of anti-NF-kB or CXCR2 combined with ICB for advanced PCa. Together, our findings highlight a critical role of ARID1A in MDSCs recruitment and demonstrate IKKb/ARID1A/NF-kB feedback axis integrating inflammation and the immunosuppression to drive PCa metastasis.
2022-11-07 | GSE213251 | GEO
Project description:ARID1A loss shapes immunosuppression tumor microenvironment via NF-kB induced MDSC chemotaxis to promote prostate Cancer metastasis
| PRJNA811575 | ENA
Project description:ARID1A loss shapes immunosuppression tumor microenvironment via NF-kB induced MDSC chemotaxis to promote prostate Cancer metastasis [ChIP-seq]
| PRJNA811961 | ENA