PD-L1 expression in inflammatory myofibroblastic tumors

Tricia R. Cottrell, Anh T. Duong, Christopher Gocke, Haiying Xu, Aleksandra Ogurtsova, Janis M Taube, Deborah A Belchis

Research output: Contribution to journalArticle

Abstract

Inflammatory myofibroblastic tumor is a rare mesenchymal tumor occurring at many anatomic sites, with a predilection for children and young adults. Often indolent, they can be locally aggressive and can metastasize, resulting in significant morbidity and mortality. Therapeutic options are often limited. The identification of underlying kinase mutations has allowed the use of targeted therapy in a subset of patients. Unfortunately, not all tumors harbor mutations and resistance to tyrosine kinase inhibitor therapy is a potential problem. We hypothesized that these tumors may be amenable to PD-L1 therapy given the immune nature of the tumor. PD-L1 expression in inflammatory myofibroblastic tumors has not yet been defined. The purpose of this study was to explore PD-L1 expression in inflammatory myofibroblastic tumors, as adaptive PD-L1 expression is known to enrich for response to anti-PD-1/PD-L1 therapies. Expression of PD-L1 (clone SP142) was assessed in 35 specimens from 28 patients. Positivity was defined as membranous expression in ≥5% of cells and evaluated separately in tumor and immune cells. Adaptive vs. constitutive patterns of tumor cell PD-L1 expression were assessed. PD-L1 status was correlated with clinicopathologic features. CD8+ T cell infiltrates were quantified by digital image analysis. ALK status was assessed by immunohistochemistry and/or FISH. Twenty-four (69%) tumors had PD-L1(+) tumor cells and 28 (80%) showed PD-L1(+) immune cells. Most recurrent and metastatic tumors (80%) and ALK(−) tumors (88%) were PD-L1(+). Adaptive PD-L1 expression was present in 23 (96%) of PD-L1(+) tumors, which also showed a three–four fold increase in CD8+ T cell infiltration relative to PD-L1(−) tumors. Constitutive PD-L1 expression was associated with larger tumor size (p = 0.002). Inflammatory myofibroblastic tumors show frequent constitutive and adaptive PD-L1 expression, the latter of which is thought to be predictive of response to anti-PD-1. These data support further investigation into PD-1/PD-L1 blockade in this tumor type.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalModern Pathology
DOIs
StateAccepted/In press - Feb 15 2018

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Cottrell, T. R., Duong, A. T., Gocke, C., Xu, H., Ogurtsova, A., Taube, J. M., & Belchis, D. A. (Accepted/In press). PD-L1 expression in inflammatory myofibroblastic tumors. Modern Pathology, 1-9. https://doi.org/10.1038/s41379-018-0034-6