# Spatial immune profiling reveals distinct microenvironments in medullary thyroid carcinoma

**Authors:** Maria Eduarda de Castro, Gustavo Forlin de Siqueira, Jean Ferrante Mariano, Marina Malta Letro Kizys, Lucieli Ceolin, Fernando Augusto Soares, Rodrigo Natal, Humberto Carneiro, Rodrigo Nalio Ramos, Laura Sterian Ward, Niels Olsen Saraiva Camara, Cleber Pinto Camacho, Flavia de Oliveira Facuri Valente, Susan Chow Lindsey, Diego Dias dos Santos, Cristiane Damas Gil, João Roberto Maciel Martins, Rui Monteiro de Barros Maciel, Lucas Leite Cunha

PMC · DOI: 10.3389/fimmu.2025.1579205 · Frontiers in Immunology · 2025-05-21

## TL;DR

This study explores the immune environment in medullary thyroid carcinoma and finds distinct immune cell patterns that could inform future immunotherapies.

## Contribution

The study reveals a spatially distinct immune profile in medullary thyroid carcinoma, including immune cell infiltration patterns and marker expression.

## Key findings

- Normal tissues adjacent to tumors show increased CD3+, CD4+, CD8+, and CD20+ lymphocytes.
- Granzyme B+ cells are notably present at the tumor interface, especially in patients with structural disease.
- Metastatic tissues show significant enrichment of mast cells.

## Abstract

Medullary thyroid carcinoma (MTC) is a rare and aggressive thyroid cancer with a challenging prognosis. While the immune microenvironment plays a crucial role in cancer progression, its role in MTC remains underexplored compared to more common thyroid cancers.

this study investigates the immune landscape of MTC by systematically evaluating immune cell infiltration and expression of immune markers across various tissue topographies. We utilized advanced immunohistochemical techniques to analyze tissue samples from 24 MTC patients, focusing on the tumor core, interface with healthy tissue, adjacent normal thyroid tissue, and lymph node metastases.

our findings reveal a distinct immune profile with increased CD3+, CD4+, CD8+ and CD20+ lymphocytes in normal tissues adjacent to tumors and a notable presence of granzyme B+ cells in the tumor interface, particularly in patients with structural disease. Additionally, we observed a significant enrichment of mast cells in metastatic tissues.

these results highlight the complex and spatially dependent immune landscape of MTC, suggesting implications for targeted immunotherapy. This study provides novel insights into the immune microenvironment of MTC and emphasizes the need for further research to elucidate its impact on disease progression and therapeutic response.

## Linked entities

- **Proteins:** cd.3 (Cd.3 conserved hypothetical protein), CD4 (CD4 molecule), CD8A (CD8 subunit alpha), MS4A1 (membrane spanning 4-domains A1)
- **Diseases:** medullary thyroid carcinoma (MONDO:0007958), thyroid cancer (MONDO:0002108)

## 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}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}
- **Diseases:** thyroid cancer (MESH:D013964), MTC (MESH:C536914), cancer (MESH:D009369), lymph node metastases (MESH:D008207)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12133767/full.md

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12133767/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12133767/full.md

---
Source: https://tomesphere.com/paper/PMC12133767