Characterization of Altered immunity in Anaplastic Thyroid …


Rim Ouni

Department of Immunology

Dr Nurieva’s lab


• Anaplastic thyroid cancer (ATC) occurs in less than 2% of all thyroid cancer cases, and it is almost uniformly lethal with an average median survival of 6months (Manikas et al; JAMA Oncol, 2020) • ATC is very aggressive and spreads rapidly within the neck and metastasizes to distant parts of the body, which makes it resistant to standard therapy (surgery, radioactive iodine therapy and chemotherapy) (Zhang et al; EJMC, 2022) • The mutational landscape of ATC is very complex compared to other forms of thyroid cancer, including Papillary (PTC) and Follicular (FTC), due to multiple mutations in oncogenes and tumor suppressors (Cancer Genome Atlas Research N; Cell, 2014; Landa et al; JCI, 2016) • Thyroid cancers are rich in immune cells, making them a reasonable candidate for immunotherapies (Varrichi et al; IJMS 2019) • To develop new therapeutic strategies, further studies determining the immune cell composition of ATC that favors tumor progression are required

Hypothetical scheme of immune contexture of thyroid cancer (Varrichi et al; IJMS 2019)

Summary • ATC tumor microenvironment is highly enriched with exhausted CD4+ T cells expressing PD-1, LAG3 and CTLA-4 • ATC tumors are infiltrated with immunosuppressive myeloid cells, cDC2 and M2 macrophages, expressing high levels of PDL1 • Treg cells changed phenotype towards inflammatory Th17 cells in ATC

Future directions

• Assess the contribution of immune cells to ATC pathogenesis

• Evaluate the efficacy of cell-targeted and immune checkpoint blockade therapy in ATC model


Dr. RozaNurieva Dr. Sang Kim Naimah Turner William Padron

Dr. Marie-Claude Hofmann Ali Dadbin Dr. Elena Fujiwara

Dr. Stephan Lai Ying Henderson Dr. Yunyun Chen

Dr. Marc Zafereo Dr. Jennifer R Wang Dr. Maria Cabanillas Dr. Ramona Dadu

Funding: Petrick/MDA Funds: The Anaplastic Thyroid Cancer Multidisciplinary Research Project

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