title: Characterizing the immune microenvironment of malignant peripheral nerve sheath tumor by PD-L1 expression and presence of CD8+ tumor infiltrating lymphocytes.
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.
authors: Division of Surgical Oncology, Department of Surgery, University of California, Los Angeles, CA 90095, USA.
authors: Elizabeth
authors: E
authors: Shurell
authors: Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA.|UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA.
authors: Arun S
authors: AS
authors: Singh
authors: Division of Surgical Oncology, Department of Surgery, University of California, Los Angeles, CA 90095, USA.
authors: Joseph G
authors: JG
authors: Crompton
authors: Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA.
authors: Sarah
authors: S
authors: Jensen
authors: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
authors: Yunfeng
authors: Y
authors: Li
authors: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.|UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA.
authors: Sarah
authors: S
authors: Dry
authors: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.|UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA.
authors: Scott
authors: S
authors: Nelson
authors: Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA.|UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA.
authors: Bartosz
authors: B
authors: Chmielowski
authors: Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA.|UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA.
authors: Nicholas
authors: N
authors: Bernthal
authors: Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA.|UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA.
authors: Noah
authors: N
authors: Federman
authors: Department of Dermatology, University of California, Los Angeles, CA 90095, USA.|UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA.
authors: Paul
authors: P
authors: Tumeh
authors: Division of Surgical Oncology, Department of Surgery, University of California, Los Angeles, CA 90095, USA.|Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.|UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA.
authors: Fritz C
authors: FC
authors: Eilber
mesh_terms: D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009442:Neurilemmoma / Q000276:immunology* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012983:Soft Tissue Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: CD8; MPNST; PD-L1; immune microenvironment; sarcoma