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C-Myc诱导的小细胞肺癌高唾液酸化促进巨噬细胞的促肿瘤表型。

C-Myc-induced hypersialylation of small cell lung cancer facilitates pro-tumoral phenotypes of macrophages.

作者信息

Tian Lin, Li Hui, Zhao Peiyan, Liu Yan, Lu Yuanhua, Zhong Rui, Jin Yulong, Tan Tianyu, Cheng Ying

机构信息

Medical Oncology Translational Research Lab, Jilin Cancer Hospital, Changchun 130012, China.

Postdoctoral Research Workstation, Jilin Cancer Hospital, Changchun 130012, China.

出版信息

iScience. 2023 Aug 29;26(10):107771. doi: 10.1016/j.isci.2023.107771. eCollection 2023 Oct 20.

DOI:10.1016/j.isci.2023.107771
PMID:37731607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10507237/
Abstract

Immunosuppressive myeloid cell populations have been documented in small cell lung cancer (SCLC) subtypes, playing a key role in remolding the tumor microenvironment (TME). However, the cancer-associated transcriptional features of monocytes and tumor-associated macrophages (TAMs) in SCLC remain poorly understood. Herein, we analyzed the molecular features and functions of monocyte/macrophage subsets aiming to inhibit monocyte recruitment and pro-tumor behavior of macrophages. We observe that NEUROD1-high SCLC subtype (SCLC-N) exhibits subtype-specific hypersialylation induced by the unique target c-Myc (MYC) of NEUROD1. The hypersialylation can alter macrophage phenotypes and pro-tumor behavior by regulating the expression of the immune-inhibiting lectin receptors on monocyte-derived macrophages (MDMs) in SCLC-N. Inhibiting the aberrant sialic acid metabolic pathways in SCLC can significantly enhance the phagocytosis of macrophages. This study provides a comprehensive overview of the cancer-specific immune signature of monocytes and macrophages and reveals tumor-associated biomarkers as potential therapeutic targets for SCLC.

摘要

免疫抑制性髓样细胞群体已在小细胞肺癌（SCLC）亚型中得到记录，在重塑肿瘤微环境（TME）中发挥关键作用。然而，SCLC中单核细胞和肿瘤相关巨噬细胞（TAM）的癌症相关转录特征仍知之甚少。在此，我们分析了单核细胞/巨噬细胞亚群的分子特征和功能，旨在抑制单核细胞募集和巨噬细胞的促肿瘤行为。我们观察到NEUROD1高表达的SCLC亚型（SCLC-N）表现出由NEUROD1独特靶点c-Myc（MYC）诱导的亚型特异性超唾液酸化。这种超唾液酸化可通过调节SCLC-N中单核细胞衍生巨噬细胞（MDM）上免疫抑制凝集素受体的表达来改变巨噬细胞表型和促肿瘤行为。抑制SCLC中异常的唾液酸代谢途径可显著增强巨噬细胞的吞噬作用。本研究全面概述了单核细胞和巨噬细胞的癌症特异性免疫特征，并揭示了肿瘤相关生物标志物作为SCLC的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/2608c8313a30/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/e78dfe8e5640/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/652c24a736f9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/9d689b84206c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/a830defb271a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/652b95acc2e3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/1ea94936f1bc/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/13aa2679a9e0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/2608c8313a30/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/e78dfe8e5640/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/652c24a736f9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/9d689b84206c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/a830defb271a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/652b95acc2e3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/1ea94936f1bc/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/13aa2679a9e0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/10507237/2608c8313a30/gr7.jpg

相似文献

[1]
C-Myc-induced hypersialylation of small cell lung cancer facilitates pro-tumoral phenotypes of macrophages.

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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
First-line serplulimab plus chemotherapy in extensive-stage small-cell lung cancer: Updated results and biomarker analysis from the ASTRUM-005 randomized clinical trial.

Cancer Commun (Lond). 2025-8

[2]
Profiling the regulatory landscape of sialylation through miRNA targeting of CMP- sialic acid synthetase.

J Biol Chem. 2025-4

[3]
Identification of a potential sialylation-related pattern for the prediction of prognosis and immunotherapy response in small cell lung cancer.

Medicine (Baltimore). 2024-10-11

[4]
Advances in new targets for immunotherapy of small cell lung cancer.

Thorac Cancer. 2024-1

本文引用的文献

[1]
PHGDH heterogeneity potentiates cancer cell dissemination and metastasis.

Nature. 2022-5

[2]
Macrophage-Based Combination Therapies as a New Strategy for Cancer Immunotherapy.

Kidney Dis (Basel). 2021-9-28

[3]
c-Myc Targets HDAC3 to Suppress NKG2DL Expression and Innate Immune Response in N-Type SCLC through Histone Deacetylation.

Cancers (Basel). 2022-1-18

[4]
Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer.

Nat Commun. 2021-11-17

[5]
Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer.

Cancer Cell. 2021-11-8

[6]
The MYC oncogene - the grand orchestrator of cancer growth and immune evasion.

Nat Rev Clin Oncol. 2022-1

[7]
Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy.

Sci Transl Med. 2021-7-28

[8]
Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells.

Nature. 2021-7

[9]
CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance.

Cell Stem Cell. 2021-9-2

[10]
ST6GalNAc-I promotes lung cancer metastasis by altering MUC5AC sialylation.

Mol Oncol. 2021-7

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