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揭示髓系来源抑制细胞模式识别受体在癌症中的复杂性。

"Open Sesame" to the complexity of pattern recognition receptors of myeloid-derived suppressor cells in cancer.

机构信息

Department of Medicine, Section of Immunology, University of Verona, Verona, Italy.

出版信息

Front Immunol. 2023 Feb 22;14:1130060. doi: 10.3389/fimmu.2023.1130060. eCollection 2023.

Abstract

Pattern recognition receptors are primitive sensors that arouse a preconfigured immune response to broad stimuli, including nonself pathogen-associated and autologous damage-associated molecular pattern molecules. These receptors are mainly expressed by innate myeloid cells, including granulocytes, monocytes, macrophages, and dendritic cells. Recent investigations have revealed new insights into these receptors as key players not only in triggering inflammation processes against pathogen invasion but also in mediating immune suppression in specific pathological states, including cancer. Myeloid-derived suppressor cells are preferentially expanded in many pathological conditions. This heterogeneous cell population includes immunosuppressive myeloid cells that are thought to be associated with poor prognosis and impaired response to immune therapies in various cancers. Identification of pattern recognition receptors and their ligands increases the understanding of immune-activating and immune-suppressive myeloid cell functions and sheds light on myeloid-derived suppressor cell differences from cognate granulocytes and monocytes in healthy conditions. This review summarizes the different expression, ligand recognition, signaling pathways, and cancer relations and identifies Toll-like receptors as potential new targets on myeloid-derived suppressor cells in cancer, which might help us to decipher the instruction codes for reverting suppressive myeloid cells toward an antitumor phenotype.

摘要

模式识别受体是原始传感器,可引发针对广泛刺激物(包括非自身病原体相关和自身损伤相关分子模式分子)的预配置免疫反应。这些受体主要由先天髓样细胞表达,包括粒细胞、单核细胞、巨噬细胞和树突状细胞。最近的研究揭示了这些受体的新见解,它们不仅是触发针对病原体入侵的炎症过程的关键因素,而且在包括癌症在内的特定病理状态下还介导免疫抑制。髓源性抑制细胞在许多病理条件下优先扩增。这种异质性细胞群体包括免疫抑制性髓样细胞,据认为与各种癌症中的预后不良和对免疫治疗的反应受损有关。识别模式识别受体及其配体增加了对免疫激活和免疫抑制性髓样细胞功能的理解,并阐明了髓源性抑制细胞与健康状态下同源粒细胞和单核细胞的区别。这篇综述总结了不同的表达、配体识别、信号通路和癌症关系,并确定 Toll 样受体作为癌症中髓源性抑制细胞的潜在新靶点,这可能有助于我们破译将抑制性髓样细胞逆转为抗肿瘤表型的指令代码。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36a9/9992799/46dc6a150c31/fimmu-14-1130060-g001.jpg

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