PD-L1 and IDO1 Are Expressed in Poorly Differentiated Thyroid Carcinoma

Abstract

Poorly differentiated thyroid carcinoma (PDTC) is an aggressive form of thyroid cancer that currently has limited effective treatment options. Immune checkpoint inhibitors (ICIs) have shown to be an effective treatment for a variety of carcinomas. In this study, we explore whether immune checkpoint pathways, such as programmed cell death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1), are activated in a cohort of patients with PDTC to determine whether ICIs may be an effective therapy for these patients. PDTC from 28 patients were stained for IDO1, PD-L1, and CD8 using immunohistochemistry. Staining was scored using an H-score, and PD-L1 and IDO1 expression was correlated with clinicopathologic characteristics. Positivity for PD-L1 and IDO1 was set at an H-score cutoff of five. Twenty-five percent (n = 7/28) of the PDTC were positive for PD-L1 expression. Twenty-nine percent (n = 2/7) of the PD-L1 positive PDTCs also co-expressed IDO1. The expression of PD-L1 in PDTC was significantly associated with tumor size and multifocality, with a non-significant trend towards associations with older age, extrathyroidal extension, presence of metastasis, higher stage, increased number of CD8+ T cells, and decreased disease-free and overall survival. PD-L1 expression occurs in a subset of PDTC, and is associated with a subset of clinical features of aggressive thyroid disease. Given the limited effective treatments for this patient population, consideration for ICIs as monotherapy or in combination with an IDO1 inhibitor should be explored as a novel treatment modality for patients with PDTC.

PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

“…In recent years, a few studies investigating PD‐L1 in thyroid cancer have established a frequency of expression ranging between 23% and 87% in thyroid carcinoma . Interestingly, some studies reported diffuse and strong PD‐L1 expression in anaplastic thyroid carcinoma . Anti–PD‐L1 immunotherapy may offer a novel means for managing unresponsive patients afflicted by this particularly aggressive thyroid cancer.…”

Do we need PD‐L1 as a biomarker for thyroid cytologic and histologic specimens?

“…A recent meta‐analysis by Aghajani et al, which included 721 patients with nonmedullary thyroid carcinomas, showed a significant association between PD‐L1 positivity, tumor recurrence, and poor survival, suggesting a possible role of PD‐L1 as a prognostic marker (akin to BRAF V600E). Conversely, although PD‐L1 in PDTC was significantly associated with tumor size and multifocality, there was only a nonsignificant trend toward an association with prognostic factors . Thus, prospective clinical trials are needed to support these findings for different thyroid cancers.…”

“…Cunha et al analyzed 293 PTCs/follicular thyroid carcinomas, 114 benign nodules, and 5 normal tissues and concluded that PD‐L1 (B7‐H1) immunohistochemistry did not have diagnostic utility . The study by Rosenbaum et al on poorly differentiated thyroid carcinoma (PDTC) also supports the concept that PD‐L1 staining is often limited, focal, and heterogeneous, limiting its use as a diagnostic marker . Fu et al analyzed the expression of PD‐L1 in 52 NIFTPs, 45 invasive encapsulated follicular variants of PTC (EFVPTCs), and 40 benign nodules .…”

“…Although a strong staining may be informative and potentially relevant, a negative staining should be taken with caution, especially on cytology. Therefore, although immunocytochemistry for thyroid FNAs (eg, HBME‐1, galectin‐3, BRAF V600E) is used by some laboratories, it is not widely accepted by most laboratories, and PD‐L1 immunocytochemistry is even more questionable given the finding that its expression is often focal and heterogeneous . Also, an important pitfall (false‐positive) for PD‐L1 as a marker of neoplasia/malignancy for thyroid includes autoimmune thyroid diseases (AITDs) such as Graves and Hashimoto, in which reactive thyroid follicular cells (TFCs) are well recognized as mimics of PTC that may result in a false‐positive diagnosis.…”

“…14 The study by Rosenbaum et al on poorly differentiated thyroid carcinoma (PDTC) also supports the concept that PD-L1 staining is often limited, focal, and heterogeneous, Cancer Cytopathology March 2020 limiting its use as a diagnostic marker. 15 Fu et al analyzed the expression of PD-L1 in 52 NIFTPs, 45 invasive encapsulated follicular variants of PTC (EFVPTCs), and 40 benign nodules. 16 They found no significant differences in PD-L1 cytoplasmic staining between NIFTPs and benign lesions, whereas there was a significant increase in invasive EFVPTCs.…”