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

// Elizabeth Shurell 1, * , Arun S. Singh 2, 7, * , Joseph G. Crompton 1 , Sarah Jensen 2 , Yunfeng Li 3 , Sarah Dry 3, 7 , Scott Nelson 3, 7 , Bartosz Chmielowski 2, 7 , Nicholas Bernthal 4, 7 , Noah Federman 2, 7 , Paul Tumeh 5, 7 , Fritz C. Eilber 1, 6, 7 1 Division of Surgical Oncology, Department of Surgery, University of California, Los Angeles, CA 90095, USA 2 Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA 3 Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA 4 Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA 5 Department of Dermatology, University of California, Los Angeles, CA 90095, USA 6 Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA 7 UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA * indicates co-first authors Correspondence to: Fritz C. Eilber, email: fceilber@mednet.ucla.edu 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.