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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Differentiated Thyroid Cancer Is Associated With Sex-specific Immune Response.

Leila Shobab1, Jennifer Simpson2, Matthew McCoy3

  • 1Department of Medicine, Division of Endocrinology, MedStar Washington Hospital Center, Washington, DC 20010, USA.

Journal of the Endocrine Society
|December 8, 2025
PubMed
Summary
This summary is machine-generated.

Men with thyroid cancer (TC) have a more immunosuppressive tumor microenvironment (TME) with higher dividing natural killer (NK) cells and CD8 T cells expressing Tigit. Understanding these sex differences in immune cells is crucial for developing targeted TC therapies.

Keywords:
sex difference in thyroid cancerthyroid cancer immune responsethyroid cancer tumor microenvironment

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Area of Science:

  • Immunology
  • Oncology
  • Genomics

Background:

  • Thyroid cancer (TC) demonstrates significant sex-based disparities in incidence, progression, and patient outcomes.
  • Women of reproductive age generally experience more favorable prognoses compared to men with TC.
  • This study focuses on elucidating sex differences in immune cell dynamics within the peripheral blood and tumor microenvironment (TME) of TC patients.

Purpose of the Study:

  • To investigate and compare the sex-specific immune cell composition and gene expression profiles in the TME of thyroid cancer.
  • To identify potential sex-based differences in immune cell frequencies and their functional implications in TC.
  • To explore the role of immune-related gene expression in sex disparities observed in TC.

Main Methods:

  • A prospective study involving 27 patients (16 females, 11 males) undergoing thyroidectomy for TC or high-risk nodules.
  • Immune cell analysis of collected tissue and blood samples using flow cytometry and spatial transcriptomics.
  • Differential gene expression analysis of immune-related genes using DESeq2 and comparison of immune cell frequencies between sexes.

Main Results:

  • Males exhibited higher frequencies of dividing natural killer (NK) cells and Tigit+ CD8 T cells within the TME.
  • Females showed a trend towards higher frequencies of mature NK cells and CD8 T cells.
  • Spatial transcriptomics revealed reduced HLA-DRB expression (antigen presentation) in males and differential expression of LAG3, IFNAR1, CD68, and B2M in the TME compared to females.

Conclusions:

  • Significant sex-based differences in immune cell composition and gene expression exist within the TC TME.
  • Males present with a more immunosuppressive profile, characterized by higher inhibitory immune markers and lower functional NK cell frequencies.
  • Incorporating sex-specific immune profiles is essential for developing targeted therapies for advanced TC.