PD-L1 Expression Varies in Thyroid Cancer Types and Is Associated with Decreased Progression Free Survival (PFS) in
Leila Shobab1, Deema Al-Souri1, Liza Mathews-Kim2
1Department of Medicine, Division of Endocrinology, MedStar Washington Hospital Center, Washington, DC 20010, USA.
Background:
Thyroid cancer (TC) remains a significant clinical challenge worldwide, with a subset of patients facing aggressive disease progression and therapeutic resistance. Immune checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1) have emerged as promising therapeutic approaches for various malignancies, yet their efficacy in TC remains uncertain. The objective of this study was to investigate PD-L1 expression in aggressive TC and its association with histological subtypes, molecular mutation, and progression-free survival.
Methods:
This is a retrospective study of patients with advanced TC seen in two tertiary health care centers. Included in this study were patients with advanced TC with recurrence or progression on therapy for whom tumor molecular profiling and PD-L1 status were available. Kaplan-Meier estimators were utilized to analyze the progression-free survival (PFS) between patients with PD-L1 positive and negative status in Anaplastic TC (ATC) subgroup.
Results:
A total of 176 patients with advanced thyroid cancer were included (48.9% female). Of the patients, 13 had ATC, 11 Medullary TC (MTC), 81 Papillary TC Classic Variant (PTCCV), 20 Follicular TC (FTC), 8 Oncocytic TC (OTC), 10 Poorly Differentiated TC (PDTC), and 30 had the Papillary TC Follicular Variant (PTCFV). BRAF mutation was present in 41%, TERT in 30%, RAS in 19%, TP53 in 10%, and RET in 8.6% of patients. PD-L1 positivity was significantly different across different TC types and histological subtypes (p < 0.01): Patients with OTC had the highest frequency of PD-L1 positivity (71%), followed by ATC (69%), PTCCV (28.5%), and FTC (11%). Patients with MTC and PTCFV did not exhibit any PD-L1 positivity. TP53 mutation was positively associated with PD-L1 expression (21.6% vs. 7.5%, p = 0.03), and RAS mutation was negatively associated with PD-L1 expression (8.1% vs. 24.2% p = 0.04). Among patients with ATC, positive PD-L1 expression was associated with lower PFS (p = 0.002).
Conclusions:
PD-L1 expression varies across different TC types and histological subtypes and may be modulated by the mutational landscape. PD-L1 expression in ATC is associated with shorter PFS. Follow up studies are warranted to elucidate the molecular mechanism driving the observed differences in immune pathways, potentially paving the way for the development of more effective and personalized immune therapies for patients with aggressive TC.
Insights
Programmed death-ligand 1 (PD-L1) expression varies in thyroid cancer (TC) subtypes and is linked to mutations. In Anaplastic TC (ATC), PD-L1 positivity correlates with shorter progression-free survival, suggesting potential for targeted immunotherapies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Thyroid cancer (TC) presents a significant clinical challenge, particularly aggressive forms resistant to therapy.
- Immune checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1) show promise in various cancers, but their role in TC is unclear.
- Understanding PD-L1 expression is crucial for developing effective immunotherapies for advanced TC.
Purpose of the Study:
- To investigate programmed death-ligand 1 (PD-L1) expression in aggressive thyroid cancer (TC).
- To analyze the association of PD-L1 expression with histological subtypes and molecular mutations in TC.
- To evaluate the impact of PD-L1 status on progression-free survival (PFS) in advanced TC.
Main Methods:
- Retrospective analysis of 176 advanced thyroid cancer patients from two tertiary centers.
- Tumor molecular profiling and PD-L1 status assessment were performed.
- Kaplan-Meier estimators were used to compare progression-free survival (PFS) based on PD-L1 status in the Anaplastic TC (ATC) subgroup.
Main Results:
- PD-L1 positivity varied significantly across TC types (p < 0.01), with highest frequencies in Oncocytic TC (71%) and ATC (69%).
- TP53 mutation positively correlated with PD-L1 expression, while RAS mutation showed a negative association.
- In the ATC subgroup, positive PD-L1 expression was significantly associated with shorter PFS (p = 0.002).
Conclusions:
- PD-L1 expression in thyroid cancer is heterogeneous, influenced by histological type and molecular mutations.
- PD-L1 expression in Anaplastic TC (ATC) is linked to poorer progression-free survival.
- Further research into the molecular mechanisms of PD-L1 regulation in TC is needed to guide personalized immune therapy development.
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