Expression and prognostic impact of immune modulatory molecule PD-L1 in meningioma.
While immunotherapy may offer promising new approaches for high grade meningiomas, little is currently known of the immune landscape in meningiomas. We sought to characterize the immune microenvironment and a potentially targetable antigen mesothelin across WHO grade I-III cases of meningiomas, and how infiltrating immune populations relate to patient outcomes. Immunohistochemistry was performed on tissue microarrays constructed from 96 meningioma cases. The cohort included 16 WHO grade I, 62 WHO grade II, and 18 WHO grade III tumors. Immunohistochemistry was performed using antibodies against CD3, CD8, CD20, CD68, PD-L1, and mesothelin. Dual staining using anti-PD-L1 and anti-CD68 antibodies was performed, and automated cell detection and positive staining detection algorithms were utilized. Greater degree of PD-L1 expression was found in higher grade tumors. More specifically, higher grade tumors contained increased numbers of intratumoral CD68-, PD-L1+ cells (p = 0.022), but did not contain higher numbers of infiltrating CD68+, PD-L1+ cells (p = 0.30). Higher PD-L1+/CD68- expression was independently predictive of worse overall survival in our cohort when accounting for grade, performance status, extent of resection, and recurrence history (p = 0.014). Higher expression of PD-L1+/CD68- was also present in tumors that had undergone prior radiotherapy (p = 0.024). Approximately quarter of meningiomas overexpressed mesothelin to levels equivalent to those found in pancreatic carcinomas and malignant mesotheliomas. The association with poor survival outcomes in our study suggests that PD-L1 may play a significant biologic role in the aggressive phenotype of higher grade meningiomas. Thus, immunotherapeutic strategies such as checkpoint inhibition may have clinical utility in PD-L1 overexpressing meningiomas.
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA. seunggu.han@ucsf.edu.
Seunggu J
SJ
Han
Department of Pathology, Division of Neuropathology, University of California, San Francisco, San Francisco, CA, USA.
Gerald
G
Reis
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.
Gary
G
Kohanbash
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.
Shruti
S
Shrivastav
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.
Stephen T
ST
Magill
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.|Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Annette M
AM
Molinaro
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.
Michael W
MW
McDermott
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.
Philip V
PV
Theodosopoulos
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.
Manish K
MK
Aghi
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.
Mitchel S
MS
Berger
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.
Nicholas A
NA
Butowski
Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA.
Igor
I
Barani
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.|Department of Pathology, Division of Neuropathology, University of California, San Francisco, San Francisco, CA, USA.
Joanna J
JJ
Phillips
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.|Department of Pathology, Division of Neuropathology, University of California, San Francisco, San Francisco, CA, USA.
Arie
A
Perry
Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA.
Hideho
H
Okada
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008577:Meningeal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D008579:Meningioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D000090204:Mesothelin; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D055815:Young Adult
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D058851:GPI-Linked Proteins; D000090204:Mesothelin
B7-H1; Checkpoint; Immunotherapy; Lymphocyte; Macrophage; Meningioma; PD-L1