# 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.

## Key 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.