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NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma

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Název: NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma
Autoři: Jiaxin Yin, Yuxiao Song, Yang Fu, Jun Wang, Zhimin Zhang, Shasha Ruan, Gaoli Liu, Bicheng Zhang
Zdroj: Cancer Immunol Immunother
Cancer Immunology, Immunotherapy, Vol 74, Iss 1, Pp 1-18 (2024)
Informace o vydavateli: Springer Science and Business Media LLC, 2024.
Rok vydání: 2024
Témata: Lung adenocarcinoma, Male, Lung Neoplasms, Adenocarcinoma of Lung, LILRB4, NF-κB, Mice, Cell Line, Tumor, Tumor-Associated Macrophages, Humans, Animals, Receptors, Immunologic, RC254-282, NLRP12, Feedback, Physiological, Mice, Knockout, Membrane Glycoproteins, Tumor-associated macrophages, Research, NF-kappa B, Intracellular Signaling Peptides and Proteins, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Mice, Inbred C57BL, C1qA, Female, Signal Transduction
Popis: The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs protumor polarization. Our study explored the unique positive feedback loop between inflammasome and complement in TAMs. The present study identified NOD-like receptors family pyrin domain containing 12 (NLRP12) formed positive feedback with C1qA and drove TAMs protumor polarization via the LILRB4/NF-κB pathway. In addition, NLRP12 was predominantly expressed in TAMs and was associated with poorer prognosis in lung adenocarcinoma (LUAD) patients. Knocking down LILRB4 inhibited TAMs protumor polarization. NLRP12-overexpressing TAMs promoted tumor cells' malignant progression and inhibited T cells' proliferation and cytotoxic function. Lastly, NLRP12 knockout (NLRP12-/-) reversed macrophage polarization, enhanced T-cell anti-tumor immunity, and suppressed tumor growth. Our findings highlighted the essential role of NLRP12/C1qA positive feedback loop and the LILRB4/NF-κB pathway in promoting TAMs protumor polarization. Inhibition of NLRP12 suppressed tumor development and promoted immune response. NLRP12 may be a promising target for LUAD immunotherapy.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1432-0851
DOI: 10.1007/s00262-024-03880-6
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39527158
https://doaj.org/article/4960a066e5b04f439bbb76f6b8ffbc78
Rights: CC BY NC ND
Přístupové číslo: edsair.doi.dedup.....141a53db9b5469c2d56261412e8e242b
Databáze: OpenAIRE
Popis
Abstrakt:The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs protumor polarization. Our study explored the unique positive feedback loop between inflammasome and complement in TAMs. The present study identified NOD-like receptors family pyrin domain containing 12 (NLRP12) formed positive feedback with C1qA and drove TAMs protumor polarization via the LILRB4/NF-κB pathway. In addition, NLRP12 was predominantly expressed in TAMs and was associated with poorer prognosis in lung adenocarcinoma (LUAD) patients. Knocking down LILRB4 inhibited TAMs protumor polarization. NLRP12-overexpressing TAMs promoted tumor cells' malignant progression and inhibited T cells' proliferation and cytotoxic function. Lastly, NLRP12 knockout (NLRP12-/-) reversed macrophage polarization, enhanced T-cell anti-tumor immunity, and suppressed tumor growth. Our findings highlighted the essential role of NLRP12/C1qA positive feedback loop and the LILRB4/NF-κB pathway in promoting TAMs protumor polarization. Inhibition of NLRP12 suppressed tumor development and promoted immune response. NLRP12 may be a promising target for LUAD immunotherapy.
ISSN:14320851
DOI:10.1007/s00262-024-03880-6