PD‐L1 and PD‐1 expression in thyroid follicular epithelial dysplasia: Hashimoto thyroiditis related atypia and potential papillary carcinoma precursor

Abstract

Programmed cell death ligand (PD-L1)/PD-1 expression has been studied in a variety of cancers and blockage of PD-L1/PD-1 pathway is a cornerstone of immunotherapy. We studied PD-L1/PD-1 immunohistochemical expression in 47 thyroid gland specimens in groups of (1) Hashimoto thyroiditis (HT) only; (2) HT and follicular epithelial dysplasia (FED); and (3) HT, FED, and papillary thyroid carcinoma (PTC). PD-1 positivity was found in immune cells, namely in lymphocytes, macrophages, and plasma cells with mean values for lymphocytes and macrophages 9% in HT group, 4% in FED group, and 4% in PTC group. PD-L1 positivity was identified in both immune cells and in the normal epithelial cells. In the HT group, mean PD-L1 staining on immune cells was 6%, in FED group 5%, and in PTC group 7%. The mean PD-L1 staining on the epithelial cells in the inflammatory parenchyma was 11.7% in HT, 13.4% in FED, and 8.3% in PTC group. The mean PD-L1 staining of FED foci was 47.2% in FED group and 33.6% in PTC group. The mean tumor proportion score (TPS) was 10.4%, and the mean combined positive score (CPS) was 15.5. At the moment, PTC is not a target of immunotherapy. However, understanding the complex issue of concurrent inflammation and autoimmunity can importantly influence the cancer treatment in future.

Towards an era of precise diagnosis and treatment: Role of novel molecular modification-based imaging and therapy for dedifferentiated thyroid cancer

“…A recent phase II single-arm study of spartalizumab, a PD-1 inhibitor, showed a favorable ORR of 29% in PD-L1 (+) vs. 0% in PD-L1 (–) ATC patients (n=42); the highest rate of response was observed in the subset of patients with PD-L1 ≥ 50% (6/17; 35%); median PFS and OS are 1.7 and 5.9 months, respectively; OS also correlated with PD-L1 status, with a median OS of 1.6 months in patients with PD-L1 < 1%, compared with not yet reached in PD-L1(+) patients ( 106 ). Notably, the co-existence of thyroid cancer with thyroiditis is common, and PD-L1 expression can also be detected in inflammatory thyroid tissue ( 107 ). Therefore, it should be cautious to interpret PD-L1 expression for thyroid cancer combined with thyroiditis and more investigations are needed.…”

Mechanism of immune escape mediated by receptor tyrosine kinase KIT in thyroid cancer

“…In addition, its ligand PD‐L1 is also abnormally high expressed in tumor cells, which is also a major factor promoting tumor immune escape ability 12 . The expression of PD‐L1/PD‐1 in various cancers has been studied, and blocking the PD‐L1/PD‐1 pathway is the cornerstone of immunotherapy 13 . Therefore, it is important to understand the specific mechanism of PD‐L1 in immune escape in TC.…”

“… 12 The expression of PD‐L1/PD‐1 in various cancers has been studied, and blocking the PD‐L1/PD‐1 pathway is the cornerstone of immunotherapy. 13 Therefore, it is important to understand the specific mechanism of PD‐L1 in immune escape in TC.…”