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空间免疫图谱揭示了甲状腺髓样癌中不同的微环境。

Spatial immune profiling reveals distinct microenvironments in medullary thyroid carcinoma.

作者信息

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

机构信息

Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.

Pathology Division, D'Or Research Institute, Rede D'Or Hospitals Network, São Paulo, Brazil.

出版信息

Front Immunol. 2025 May 21;16:1579205. doi: 10.3389/fimmu.2025.1579205. eCollection 2025.

Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

DISCUSSION

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.

摘要

引言

甲状腺髓样癌(MTC)是一种罕见且侵袭性强的甲状腺癌,预后具有挑战性。虽然免疫微环境在癌症进展中起着关键作用,但与更常见的甲状腺癌相比,其在MTC中的作用仍未得到充分探索。

方法

本研究通过系统评估不同组织部位的免疫细胞浸润和免疫标志物表达,来研究MTC的免疫格局。我们利用先进的免疫组织化学技术分析了24例MTC患者的组织样本,重点关注肿瘤核心、与健康组织的交界处、相邻正常甲状腺组织和淋巴结转移灶。

结果

我们的研究结果显示出一种独特的免疫特征,在肿瘤邻近的正常组织中CD3 +、CD4 +、CD8 +和CD20 +淋巴细胞增加,在肿瘤界面尤其是结构病变患者中显著存在颗粒酶B +细胞。此外,我们在转移组织中观察到肥大细胞显著富集。

讨论

这些结果突出了MTC复杂且空间依赖性的免疫格局,提示了靶向免疫治疗的意义。本研究为MTC的免疫微环境提供了新的见解,并强调需要进一步研究以阐明其对疾病进展和治疗反应的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edfe/12133767/7e5cb4e69da2/fimmu-16-1579205-g001.jpg

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