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

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

doi:10.1016/j.isci.2023.107771

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

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

Authors

Lin Tian^{1

2

3}, Hui Li^{1

3}, Peiyan Zhao^{1

3}, Yan Liu^{1

3}, Yuanhua Lu^{1

2

3}, Rui Zhong^{1

3}, Yulong Jin¹, Tianyu Tan⁴, Ying Cheng^{1

3

5}

Affiliations

¹ Medical Oncology Translational Research Lab, Jilin Cancer Hospital, Changchun 130012, China.
² Postdoctoral Research Workstation, Jilin Cancer Hospital, Changchun 130012, China.
³ Jilin Provincial Key Laboratory of Molecular Diagnostics for Lung Cancer, Jilin Cancer Hospital, Changchun 130012, China.
⁴ Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and The First Affliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
⁵ Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun 130012, China.

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.

Keywords: Biochemistry; Cancer; Cell biology; Immunology.