Dissecting Early-Stage Tumor Microenvironment with Niche-Labeling
HUANG Hanying, ZHAO Chuang, TAN Zhihong, TIAN Lin*
Tumor represents a malignant ecosystem, composed not only of transformed cancer cells but also of stromal cells, including fibroblasts, endothelial cells, pericytes, tissue-resident cells, and various immune cells. These stromal cells, which constitute the TME (tumor microenvironment), play critical roles in tumor initiation, progression, metastasis, and therapeutic resistance, rather than merely acting as bystanders. Most preclinical and clinical studies on the TME focus on overt tumors, where malignant biopsies are dissected for immunostaining or single-cell multi-omics profiling. However, the TME at late stages becomes exceedingly complex, rendering many therapeutic strategies ineffective. Therefore, it is imperative to investigate the interactions between cancer cells and tumor stroma at much earlier stages, ideally from tumor initiation or cancer cell micro-clusters. Fluorescently labeling or biochemically tagging stromal cells that are in proximity to or interact with cancer cells during tumor progression presents promising approaches for studying the evolution of aggressive tumor ecosystems and holds the potential to identify novel therapeutic targets for emerging TME. This review provides an overview of various niche-labeling techniques for studying tumor microenvironment, discusses how these systems have been applied to identify novel tumor-stroma interactions, and offers insights into combining these tools with autochthonous tumor models.
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