Comprehensive screening for PD-L1 expression in thyroid cancer

Abstract

PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142). In addition, we analyzed the relationships between PD-L1 expression and clinicopathologic factors, including TERT promoter, BRAF status and disease progression. Tumoral PD-L1 was expressed in 6.1% of papillary thyroid carcinomas, 7.6% of follicular thyroid carcinomas and 22.2% of anaplastic thyroid carcinomas. The distribution of PD-L1 positivity was different according to cancer histology types (P < 0.001). All PD-L1-positive cases of follicular thyroid carcinoma and anaplastic thyroid carcinoma showed strong intensity. The proportions of positivity in PD-L1 positive anaplastic thyroid carcinomas were more than 80%. PD-L1 in immune cells was positive in 28.5% of papillary thyroid carcinoma, 9.1% of follicular thyroid carcinomas and 11.1% of anaplastic thyroid carcinomas. There was no significant association between clinicopathologic variables, disease progression, oncogenic mutation and PD-L1 expression. PD-L1 was highly expressed in a subset of patients with advanced thyroid cancer, such as follicular and anaplastic thyroid carcinoma. Identification of PD-L1 expression may have direct therapeutic relevance to patients with refractory thyroid cancer.

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

“…However, the authors failed to demonstrate association between PD-L1 expression and clinicopathological variables of aggressiveness (Ahn et al 2017). These results were confirmed by Zwaenepoel and coworkers, who found PD-L1 expression in 28.6% of anaplastic thyroid cancer (Zwaenepoel et al 2017).…”

“…Ahn and coworkers observed that PD-L1 was more frequently expressed among anaplastic thyroid cancer, suggesting that PD-L1 expression was a late event in thyroid carcinogenesis (Ahn et al 2017). However, the authors failed to demonstrate association between PD-L1 expression and clinicopathological variables of aggressiveness (Ahn et al 2017).…”

Very low expression of PD-L1 in medullary thyroid carcinoma

“…Regarding thyroid tumors, a few papers have reported on PD-L1 expression in thyroid (Cunha et al 2013, Angell et al 2014, Wu et al 2015, Bastman et al 2016, Chowdhury et al 2016, Ahn et al 2017, Shi et al 2017). With the exception of two studies on anaplastic (undifferentiated) thyroid carcinoma (ATC) (Wu et al .…”

Immune responses in the thyroid cancer microenvironment: making immunotherapy a possible mission

“…PD-L1, the ligand for PD-1 is expressed by several types of thyroid cancers, albeit at low frequencies. Notably, out of 407 primary thyroid cancers, there was low-to-modest expression of PD-L1 in 6.1, 7.6 and 22.2% of papillary, follicular and anaplastic thyroid carcinomas, respectively 24:12 (Ahn et al 2017). Similarly, a relatively higher frequency of expression on anaplastic thyroid cancers was found by another group (Zwaenepoel et al 2017).…”