Inflammatory and immune checkpoint signatures in thyroid cancer: IHC profiling of IL-6 and its inducer PDL1 distinguishes histopathological subtypes and reflects tumor aggressiveness

This retrospective cross-sectional study evaluated the immunohistochemical (IHC) expression of interleukin‑6 (IL-6) and programmed death ligand 1 (PDL1) in thyroid carcinoma (TC; 100 cases) versus non-neoplastic/benign thyroid lesions (15 cases). IL-6 and PDL1 were assessed on tissue microarrays using an immunoreactive score (low < 6 or high ≥ 6). IL-6 and PDL1 positivity was significantly higher in TCs (IL-6: 57% vs 6.7%; PDL1: 60% vs 0%; both p ≤ 0.001). High IL-6 occurred in 39% of TCs and was associated with older age, papillary and oncocytic TCs, lymphovascular and capsular invasion, extrathyroidal extension, advanced TNM stage, multifocality, nodal metastasis, and recurrence (all p ≤ 0.05). High PDL1 occurred in 36% of TCs, was most frequent in papillary, anaplastic and oncocytic TCs, and was associated with older age, larger tumors, higher T and TNM stage, multifocality, lymphovascular emboli, extrathyroidal extension, and nodal positivity (all p ≤ 0.05). IL-6 and PDL1 showed a moderate positive correlation (r = 0.486, p ≤ 0.001). IL-6 and PD-L1 expression was significantly higher in TCs than in benign/non-neoplastic thyroid lesions and was significantly associated with biologically aggressive TCs, suggesting their potential diagnostic and prognostic utility. Their coordinated overexpression supports IL-6/PDL1 axis activation as a hallmark of high-risk TC and a potential target for combined immunomodulatory strategies.