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. 2018 Mar;29(1):59-67.
doi: 10.1007/s12022-018-9514-y.

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

Matthew W Rosenbaum  1 , Benjamin J Gigliotti  2 , Sara I Pai  2 , Sareh Parangi  2 , Heather Wachtel  2 , Mari Mino-Kenudson  3 , Viswanath Gunda  2 , William C Faquin  4
Affiliations

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

Matthew W Rosenbaum et al. Endocr Pathol. 2018 Mar.

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.

Keywords: IDO1; Immune checkpoint; Immuno-oncology; Indoleamine 2,3-dioxygenase 1; PD-L1; PD1; Poorly differentiated thyroid carcinoma; Programmed cell death ligand 1.

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Figures

Fig 1
Fig 1
Patterns of immune checkpoint expression in PDTC. Common patterns included diffuse strong expression (a), peripheral edge expression (b), lymphocytic infiltrate co-expression (c). IDO1 expression was also present in similar patterns (lymphocytic infiltrate co-expression is shown here in d). In a-c: Brown=PD-L1, Red=CD8. In d: Brown=IDO1
Fig 2
Fig 2
Kaplan Meier survival curves for disease-free survival (DFS; A) and overall survival (OS; B), by PD-L1 staining status.
Fig 3
Fig 3
Cartoon demonstrating the basic aspects of the PD-L1 and IDO1 immune checkpoint cascades. TCR: T-Cell Receptor; PD-1: Programmed Cell Death 1; PD-L1: Programmed Cell Death Ligand 1 MHC-Ag: Major Histocompatibility Complex protein-Antigen complex; IDO1:IIndoleamine 2 3-Dioxygenase 1; NK: Natural Killer.
See this image and copyright information in PMC

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