Oncotarget

Research Papers:

Characterizing the immune microenvironment of malignant peripheral nerve sheath tumor by PD-L1 expression and presence of CD8+ tumor infiltrating lymphocytes

Elizabeth Shurell, Arun S. Singh, Joseph G. Crompton, Sarah Jensen, Yunfeng Li, Sarah Dry, Scott Nelson, Bartosz Chmielowski, Nicholas Bernthal, Noah Federman, Paul Tumeh and Fritz C. Eilber _

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Oncotarget. 2016; 7:64300-64308. https://doi.org/10.18632/oncotarget.11734

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Abstract

Elizabeth Shurell1,*, Arun S. Singh2,7,*, Joseph G. Crompton1, Sarah Jensen2, Yunfeng Li3, Sarah Dry3,7, Scott Nelson3,7, Bartosz Chmielowski2,7, Nicholas Bernthal4,7, Noah Federman2,7, Paul Tumeh5,7, Fritz C. Eilber1,6,7

1Division of Surgical Oncology, Department of Surgery, University of California, Los Angeles, CA 90095, USA

2Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA

3Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA

4Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA

5Department of Dermatology, University of California, Los Angeles, CA 90095, USA

6Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA

7UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA

*indicates co-first authors

Correspondence to:

Fritz C. Eilber, email: [email protected]

Keywords: immune microenvironment, MPNST, PD-L1, CD8, sarcoma

Received: June 29, 2016     Accepted: August 16, 2016     Published: August 31, 2016

ABSTRACT

Background: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with few treatment options. Tumor immune state has not been characterized in MPNST, and is important in determining response to immune checkpoint blockade. Our aim was to evaluate the expression of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and presence of CD8+ tumor infiltrating lymphocytes (TILs) in MPNST, and correlate these findings with clinical behavior and outcome.

Results: PD-L1 staining of at least 1% was seen in 0/20 nerves, 2/68 benign lesions and 9/53 MPNST. Two of 68 benign lesions and 7/53 (13%) MPNST had at least 5% PD-L1 staining. CD8 staining of at least 5% was seen in 1/20 (5%) nerves, 45/68 (66%) benign lesions and 30/53 (57%) MPNST. PD-L1 was statistically more prevalent in MPNST than both nerves and benign lesions (p=0.049 and p=0.008, respectively). Expression of PD-1 was absent in all tissue specimens. There was no correlation of PD-L1 or CD8 expression with disease state (primary versus metastatic) or patient survival.

Methods: A comprehensive PNST tissue microarray was created from 141 surgical specimens including primary, recurrent, and metastatic MPNST (n=53), neurofibromas (n=57), schwannoma (n=11), and normal nerve (n=20). Cores were stained in triplicate for PD-L1, PD-1, and CD8, and expression compared between tumor types. These data were then examined for survival correlates in 35 patients with primary MPNST.

Conclusions: MPNST is characterized by low PD-L1 and absent PD-1 expression with significant CD8+ TIL presence. MPNST immune microenvironment does not correlate with patient outcome.


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