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Programmed death ligand 1 expression and tumor infiltrating lymphocytes in neurofibromatosis type 1 and 2 associated tumors

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Abstract

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or its ligand (PD–L1) have been shown to be effective in treating patients with a variety of cancers. Biomarker studies have found positive associations between clinical response rates and PD–L1 expression on tumor cells, as well as the presence of tumor infiltrating lymphocytes (TILs). It is currently unknown whether tumors associated with neurofibromatosis types 1 and 2 (NF1 and NF2) express PD–L1. We performed immunohistochemistry for PD–L1 (clones SP142 and E1L3N), CD3, CD20, CD8, and CD68 in NF1-related tumors (ten dermal and six plexiform neurofibromas) and NF2-related tumors (ten meningiomas and ten schwannomas) using archival formalin-fixed paraffin-embedded tissues. Expression of PD–L1 was considered positive in cases with > 5% membranous staining of tumor cells, in accordance with previously published biomarker studies. PD–L1 expression in tumor cells (using the SP142 and E1L3N clones, respectively) was assessed as positive in plexiform neurofibromas (6/6 and 5/6) dermal neurofibromas (8/10 and 6/10), schwannomas (7/10 and 10/10), and meningiomas (4/10 and 2/10). Sparse to moderate presence of CD68, CD3, or CD8 positive TILs was found in 36 (100%) of tumor specimens. Our findings indicate that adaptive resistance to cell-mediated immunity may play a major role in the tumor immune microenvironment of NF1 and NF2-associated tumors. Expression of PD–L1 on tumor cells and the presence of TILs suggest that these tumors might be responsive to immunotherapy with immune checkpoint inhibitors, which should be explored in clinical trials for NF patients.

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Acknowledgements

This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center. The NYU Experimental Pathology Immunohistochemistry Core Laboratory is supported in part by the Laura and Isaac Perlmutter Cancer Center Support Grant; NIH/NCI P30 CA016087 and the National Institutes of Health S10 Instrumentation Grants; NIH/ORIP S10 OD01058 and S10 OD018338. This study was presented in part at the Biennial 2017 Pediatric Neuro-Oncology Basic and Translational Research Conference, New York, NY, June 2017, and the Children’s Tumor Foundation 2017 NF Conference, Washington, DC, June 2017.

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Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, Department of Pediatrics, NYU Langone Health, New York, NY, USA

    Shiyang Wang & Seema Patel

  2. Division of Neuropathology, Department of Pathology, NYU Langone Health, New York, NY, USA

    Benjamin Liechty & Matija Snuderl

  3. Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA

    Jeffrey S. Weber

  4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Travis J. Hollmann

  5. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Matthias A. Karajannis

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  1. Shiyang Wang
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Correspondence to Matthias A. Karajannis.

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Wang, S., Liechty, B., Patel, S. et al. Programmed death ligand 1 expression and tumor infiltrating lymphocytes in neurofibromatosis type 1 and 2 associated tumors. J Neurooncol 138, 183–190 (2018). https://doi.org/10.1007/s11060-018-2788-6

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  • DOI: https://doi.org/10.1007/s11060-018-2788-6

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