Abstract
BackgroundMalignant 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.ResultsPD-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.MethodsA 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.ConclusionsMPNST 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.
Highlights
Malignant peripheral nerve sheath tumor (MPNST) is a soft tissue sarcoma that arises from neurofibromas, plexiform neurofibromas, or in association with a large nerve without an identifiable neurofibroma component
MPNST is characterized by low programmed death-ligand 1 (PD-L1) and absent PD-1 expression with significant CD8+ tumor infiltrating lymphocytes (TILs) presence
MPNST immune microenvironment does not correlate with patient outcome
Summary
Malignant peripheral nerve sheath tumor (MPNST) is a soft tissue sarcoma that arises from neurofibromas, plexiform neurofibromas, or in association with a large nerve without an identifiable neurofibroma component. MPNST arise spontaneously, or can occur in association with neurofibromatosis type 1 (NF-1), a www.impactjournals.com/oncotarget disease characterized by the loss of the neurofibromin tumor suppressor protein. In the case of NF1-associated MPNST, discerning malignancy from benign neurofibromas is a clinical challenge that has led to the utilization of PET imaging in tumor diagnosis [1]. Surgery is the foundation of therapy for MPNST, a major unmet clinical need is in patients who are poor surgical candidates or have relapsed/systemic disease. Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with few treatment options. 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
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