학술논문

Characterizing the immune microenvironment of malignant peripheral nerve sheath tumor by PD-L1 expression and presence of CD8+ tumor infiltrating lymphocytes
Document Type
article
Source
Oncotarget. 7(39)
Subject
Orphan Drug
Rare Diseases
Neurosciences
Neurofibromatosis
Cancer
Clinical Research
Aetiology
2.1 Biological and endogenous factors
B7-H1 Antigen
Biomarkers
Tumor
CD8-Positive T-Lymphocytes
Disease Progression
Humans
Immunohistochemistry
Lymphocytes
Tumor-Infiltrating
Neoplasm Metastasis
Neoplasm Recurrence
Local
Neurilemmoma
Proportional Hazards Models
Prospective Studies
Soft Tissue Neoplasms
Time Factors
Tissue Array Analysis
Treatment Outcome
Tumor Microenvironment
immune microenvironment
MPNST
PD-L1
CD8
sarcoma
Oncology and Carcinogenesis
Language
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.