Single-cell Transcriptomics Identify a Novel Macrophage Population Associated with Bone Invasion in Pituitary Neuroendocrine Tumors

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Date 2025 Jan 26

PMID 39865310

Authors

Xinzhi Wu

Xueshuai Han

Haibo Zhu

Mingxuan Li

Lei Gong

Sicheng Jing

Weiyan Xie

Zhaoqi Liu

Chuzhong Li

Yazhuo Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Bone-invasive Pituitary Neuroendocrine Tumors (BI PitNETs) epitomize an aggressive subtype of pituitary tumors characterized by bone invasion, culminating in extensive skull base bone destruction and fragmentation. This infiltration poses a significant surgical risk due to potential damage to vital nerves and arteries. However, the mechanisms underlying bone invasion caused by PitNETs remain elusive, and effective interventions for PitNET-induced bone invasion are lacking in clinical practice.

Methods: In this study, we performed single-cell (n = 87,287) RNA sequencing on 10 cases of bone-invasive PitNETs and 5 cases of non-bone-invasion PitNETs (Non-BI PitNETs). We identified various cell types and determined their interactions through cell-cell communication analysis, which was further validated experimentally.

Results: We identified a novel TNF-α TAM macrophage subset. BI PitNETs showed increased IL-34 secretion, impacting TNF-α TAMs via the IL34/CSF1R axis, leading to TNF-α production. TNF-α TAMs, in turn, communicate with CD14 monocytes to promote their differentiation into osteoclasts and leading to bone invasion. In addition, we defined a gene signature for TNF-α TAM to guide the clinical prognosis prediction of BI PitNETs.

Conclusions: Our study elucidates the tumor microenvironment changes in bone invasion and identifies the critical role of TNF-α TAMs in promoting bone invasion of PitNETs, laying a foundation for developing new molecular markers or therapeutic agents targeting BI PitNETs.

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