Tumor-Induced Rewiring of Splenic Niches: from Immune Organ to Cancer Accomplice

TL;DR

This review explains how tumors can change the spleen's function, turning it from an immune defender into a helper for cancer growth and spread.

Contribution

The paper highlights the spleen's role in tumor progression and its potential as a therapeutic target in oncology.

Findings

Tumors can remotely alter splenic niches through soluble mediators, promoting immune evasion and metastasis.

Splenic hematopoietic stem cells shift toward myeloid and erythroid extramedullary hematopoiesis under tumor influence.

Spleen-targeted nanoplatforms show promise for delivering immunomodulatory therapies with greater precision.

Abstract

The spleen is the largest secondary lymphoid organ in humans. Beyond its classical role in clearance of senescent erythrocytes, it functions as a pivotal node in systemic immune surveillance. Emerging evidence indicates that tumor can remotely remodel splenic niches through a spectrum of soluble mediators, thereby accelerating tumor initiation and progression. Tumor-derived signals divert splenic hematopoietic stem and progenitor cells (HSPCs) toward myeloid- and erythroid-biased extramedullary hematopoiesis (EMH), expanding myeloid-derived suppressor cells (MDSCs) and erythroid progenitor cells (EPCs) that collectively foster immune evasion and metastatic cascades. Consequently, splenic resident immune cells, stromal cells and EMH-related pathways have surfaced as actionable therapeutic targets. In parallel, bidirectional crosstalk between the autonomic nervous system and splenic immunity fine-tunes homeostasis, systemic inflammation and antitumor responses—fueling rising interest in splenic neuromodulation as a therapeutic strategy. In addition, spleen-targeted nanoplatforms are emerging as promising tools to deliver immunomodulatory payloads with improved precision. Nonetheless, inherent structural and functional disparities between human and murine spleens complicate clinical translation of pre-clinical findings. This review provides a concise overview of human lymphoid organs and their functions, with a particular focus on splenic anatomy, cellular composition, and neural regulation. It further delineates tumor-induced splenic rewiring and discusses the prospects of exploiting the spleen as both a biomarker and a therapeutic target in oncology.

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