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

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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.

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Funding

This work is supported by the NIH/NIDCR R01DE025340 (WCF and SIP), NIH 1R01CA149738-01 (SP), NIH 5T32DK00702842 (BJG), and Stand Up To Cancer-American Cancer Society Dream Team Translation Research Grant (MMK).

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Authors and Affiliations

  1. Department of Pathology, Massachusetts General Hospital, Warren 219, 55 Fruit Street, Boston, MA, 02114, USA

    Matthew W. Rosenbaum, Mari Mino-Kenudson & William C. Faquin

  2. Department of Surgery, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA

    Benjamin J. Gigliotti, Sara I. Pai, Sareh Parangi, Heather Wachtel & Viswanath Gunda

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  1. Matthew W. Rosenbaum
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  2. Benjamin J. Gigliotti
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  3. Sara I. Pai
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Correspondence to Matthew W. Rosenbaum or William C. Faquin.

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Rosenbaum, M.W., Gigliotti, B.J., Pai, S.I. et al. PD-L1 and IDO1 Are Expressed in Poorly Differentiated Thyroid Carcinoma. Endocr Pathol 29, 59–67 (2018). https://doi.org/10.1007/s12022-018-9514-y

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