Dissertations and Theses (Open Access)

Author ORCID Identifier

0000-0002-5589-8220

Date of Graduation

8-2026

Document Type

Thesis (MS)

Program Affiliation

Immunology

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Roza Nurieva

Committee Member

Seyed Moghaddam

Committee Member

Pamela Wenzel

Committee Member

Anastasios Maniakas

Committee Member

Alexandre Reuben

Abstract

Anaplastic thyroid cancer (ATC) accounts for half of all thyroid cancer-related deaths. Unlike other subtypes, women do not have a higher incidence, and the average patient age is 65 years old. Extensive immunoprofiling of the tumor microenvironment (TME) using single-cell RNA sequencing (sc-RNA-seq) has recently shown that, while immunosuppressive, ATC exhibits a higher immune infiltration than papillary thyroid cancer (PTC). This could be a therapeutic advantage for immunotherapy treatments. Male ATC patients have more aggressive growth; however, no further research has gone into sexual dimorphism. This thesis aims to elucidate on it using a preclinical murine model of ATC in C57BL/6 mice. We found sexual dimorphism in tumor growth and TME composition in young mice using orthotopic and subcutaneous models. The female TME had significantly higher anti-tumor immune infiltrations (B cells, CD8+ T cells and N1 neutrophils), while males had a higher T cell exhaustion, T regulatory cells (Tregs), and M2 macrophages. Sexual dimorphism reduced with age, as seen in our subcutaneous aged ATC mouse cohort (60w). The TME in this group was immunosuppressive with a prevalence in myeloid composition. Cell depletions revealed that CD8+ T cells and macrophages were the main players in females and males, respectively. Lastly, we determined a possible role of the microbiome in sexual dimorphism by applying an FMT engraftment with the opposite sex.

Keywords

Anaplastic Thyroid Cancer, tumor microenvironment, microbiome, sexual dimorphism, aging

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Available for download on Thursday, August 05, 2027

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