PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma: A Multi-institutional Study

Area of Science:

• Oncology
• Immunotherapy
• Thyroid Cancer Research

Background:

• Anti-programmed death (PD) immunotherapy is under investigation for anaplastic thyroid carcinoma (ATC).
• Tumor cell surface PD-L1 expression is a predictive biomarker for anti-PD immunotherapy response.
• Limited data exist on PD-L1 expression in ATC, unlike the more studied papillary thyroid carcinoma.

Purpose of the Study:

• To assess PD-L1 expression in a large cohort of anaplastic thyroid carcinomas (ATCs).
• To compare PD-L1 expression with histological patterns, specimen type, molecular profile, and patient outcomes.
• To evaluate PD-L1 expression in co-existent differentiated thyroid carcinoma (DTC) and compare it with ATC.

Main Methods:

• Retrospective multi-institutional study involving 179 ATCs across 9 Asian centers.
• PD-L1 expression assessed using the SP263 (Ventana) clone, with PD-L1 positivity defined as a tumor proportion score (TPS) ≥1%.
• Analysis included comparison with histological patterns, specimen size, BRAF V600E and TERT promoter mutation status, and patient outcomes.

Main Results:

• 73.2% of ATCs were PD-L1-positive, with a median TPS of 36% among positive cases.
• PD-L1-negative cases were more frequent in small specimens; epithelioid and pleomorphic ATCs showed higher PD-L1 expression than sarcomatoid types.
• PD-L1 expression was frequently converted from DTC-negative to ATC-positive (71% of cases); BRAF V600E mutation correlated with PD-L1 positivity.

Conclusions:

• The majority of ATCs exhibit PD-L1 expression, suggesting potential benefit from anti-PD immunotherapy.
• PD-L1 expression patterns differ between ATC and DTC, with a notable conversion in co-existing tumors.
• BRAF V600E mutation status may inform combination therapy strategies with anti-PD agents, although PD-L1 expression did not impact overall patient outcome.