Formation and remodeling of immunological niches in solid tumors: organ-specific architectures, inflammatory parallels, and therapeutic reprogramming

作者：Zhuo Zhang, Yun Dong, Jinchao Li, Youling Shi, Aihua Mei, Miaoxin Fu · 发表于：Frontiers in Immunology · 年份：2026 · DOI：10.3389/fimmu.2026.1903920 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Cancer Cells and Metastasis

Tumor immunity is increasingly understood not only through the cellular composition of the tumor microenvironment, but also through spatially organized local niches that can help determine where immune recognition is initiated, constrained, suppressed, or therapeutically restored. This review develops an organ-conditioned and evidence-graded framework for tumor immunological niches as spatially localized, interaction-dependent, functionally consequential, and dynamically remodeled units. Rather than reproducing a general taxonomy of cancer immune niches, we focus on how shared niche-forming mechanisms are implemented differently by organ-specific tissue rules. We first distinguish the niche concept from broad tumor microenvironment descriptions, immune infiltration, immune compartments, and tertiary lymphoid structures. We then propose an operational evidence hierarchy that separates spatial association, recurrent interaction, functional consequence, perturbation-based validation, and therapeutic actionability. Next, we synthesize core mechanisms of niche formation, including tumor-intrinsic signaling, stromal and extracellular-matrix scaffolding, chemokine and cytokine wiring, vascular-hypoxic-metabolic boundaries, myeloid-centered suppression, and tissue-resident immune imprinting. Brain and lung tumors are treated as two organizing paradigms: immune-restricted niche architecture in the central nervous system and inflammation-primed niche architecture in the lung. Oral, liv...