Exploring the Tumor Microenvironment of Anaplastic Thyroid Carcinoma and its impact on Patient Survival

Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy characterized by nearly 100% mortality and significant therapeutic challenges. This study investigated the tumour microenvironment (TME) in ATC, focusing on immune checkpoint molecules (PD-L1/PD-1), tumour-associated macrophages (TAMs), and E-cadherin expression. A retrospective cohort of 22 ATC patients treated at King George’s Medical University, Lucknow, India, between January 2017 and August 2022, was analyzed. Immunohistochemical evaluation revealed PD-L1 expression in 68.2% of cases, with a median tumour proportion score (TPS) of 50. PD-1 expression was limited to inflammatory cells. E-cadherin loss was observed in over 69% of cases, suggesting disrupted cell adhesion. TAM infiltration was elevated in 58.8% of patients and correlated significantly with PD-L1 expression (p = 0.02). Survival analysis demonstrated a mean overall survival of 3 months, with high PD-L1 expression, elevated TAM density, and increased PD-1 expression associated with shorter survival (p < 0.001). Patients expressing PD-L1 had a mean survival of 2.4 months compared to 4.1 months for those without PD-L1 expression (p < 0.05). Similarly, high PD-1 expression in inflammatory cells correlated with poorer outcomes (mean survival of 2.5 months versus 4.5 months for low expression; p = 0.03). These findings underscore the critical role of immune markers within the TME in influencing ATC prognosis. The significant associations of TAM density, PD-L1, and PD-1 expression with survival highlight the potential of targeted immunotherapeutic strategies to improve outcomes in ATC. Further research is warranted to clarify the predictive value of these markers in guiding treatment approaches.