# The Impact of Heterotopic Spleen Regeneration on Tumor Growth

**Authors:** Daria Artemova, Andrey Elchaninov, Anna Soboleva, Irina Arutyunyan, Polina Vishnyakova, Liudmila Gaydeek, Timur Fatkhudinov, Gennady Sukhikh

PMC · DOI: 10.1096/fba.2025-00254 · FASEB BioAdvances · 2026-01-09

## TL;DR

This study shows that spleen regeneration after surgery affects tumor growth by changing immune cell activity in mice.

## Contribution

The study reveals how spleen regeneration influences tumor microenvironment and immune cell infiltration.

## Key findings

- Spleen regeneration reduced tumor cell proliferation rate after 15 days.
- Regeneration increased macrophage and CD4+ T-lymphocyte infiltration into tumors.
- CD8+ T-lymphocyte infiltration was suppressed in regenerating spleen models.

## Abstract

The spleen is one of the key organs of the immune system that is involved in both innate and adaptive immunity. Splenectomy (SE) is surgery with many risks, including sepsis, thrombosis, and malignancy. In this regard, studies into the potential regeneration of the spleen and restoring its structure and functions are important. As in the past, heterotopic spleen transplantation regenerates the spleen structure after 30 days. This study assessed the impact of heterotopic spleen regeneration on tumor growth. We used two animal models. In the first, animals had SE. In the second, animals had SE and subcutaneous transplantation (ST) of spleen fragments. These animals, as well as intact animals, were transplanted under the skin with tumor cells to obtain a subcutaneous model of tumor growth. The results showed that while there was no significant effect on tumor growth at 15 days, there was a decrease in tumor cell proliferation rate. Spleen regeneration stimulated early occupancy of the tumor niche by macrophages, as well as influx of CD4+ T‐lymphocytes and B‐lymphocytes into the tumor, while infiltration of CD8+ T‐lymphocytes was suppressed. Thus, the effects of regenerating spleen on tumor growth that we have demonstrated require further investigation at longer follow‐up periods.

The present study evaluated the effect of spleen regeneration on tumor growth. Balb/c mice were divided into three groups: intact animals; animals that underwent splenectomy; animals that underwent splenectomy followed by autologous subcutaneous transplantation of spleen fragments. Then, after 30 days, all animals were injected subcutaneously with LLС‐1 cells and tumor growth was observed. We removed the animals from the experiment on Days 7, 12 and 15, and tumors were taken for further analysis.

## Full-text entities

- **Genes:** CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** thrombosis (MESH:D013927), sepsis (MESH:D018805), Heterotopic Spleen (MESH:D013160), Tumor (MESH:D009369)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12784169/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12784169/full.md

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Source: https://tomesphere.com/paper/PMC12784169