Spatial immune profiling reveals distinct microenvironments in medullary thyroid carcinoma

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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, Joao Roberto Maciel ; Maciel, Rui Monteiro de Barros ; Cunha, Lucas Leite

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 16, p. 12-pg., 2025-05-21.

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. (AU)

• FAPESP's process: 22/11509-0 - Multiple Endocrine Neoplasia type 2 (MEN 2) and Medullary Thyroid Carcinoma (TCM): new issues in developmental biology, genetics, immunology, epidemiology, mechanisms of disease and clinical management
• Grantee: Lucieli Ceolin
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/02752-6 - Multiple Endocrine Neoplasia type 2 (MEN 2) and Medullary Thyroid Carcinoma (TCM): new issues in developmental biology, genetics, immunology, epidemiology, mechanisms of disease and clinical management
• Grantee: Rui Monteiro de Barros Maciel
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/10804-9 - Multiple Endocrine Neoplasia type 2 (MEN 2) and Medullary Thyroid Carcinoma (TCM): new issues in developmental biology, genetics, immunology, epidemiology, mechanisms of disease and clinical management
• Grantee: Marina Malta Letro Kizys Polisel
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 24/01435-5 - Analysis of the immune response in the microenvironment of medullary thyroid carcinoma: from the bench to clinical applications
• Grantee: Maria Eduarda de Castro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 24/06697-8 - The immunological microenvironment of thyroid cancer and its clinical application: A comprehensive approach.
• Grantee: Lucas Leite Cunha
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/13451-0 - To study the immunological processes involved in sporadic or Multiple Endocrine Neoplasm (MEN2) related Medullary Thyroid Carcinoma (MTC) and its implications in systemic immunity and tumoral microenvironment
• Grantee: Gustavo Forlin de Siqueira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation