IMMU-16. PROGRAMMED DEATH LIGAND 1 EXPRESSION AND TUMOR INFILTRATING LYMPHOCYTES IN TUMORS ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1 AND 2

Abstract

BACKGROUND: Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or its ligand (PD-L1) have been shown to be effective in treating subsets of 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 hypothesized that NF-associated tumors may express PD-L1 and therefore might be amenable to immunotherapy with immune checkpoint inhibitors. METHODS: We performed immunohistochemistry for PD-L1 (Spring Bioscience, clone SP142), CD3, CD20, CD8, and CD68 in 17 NF1-related tumors (11 dermal neurofibromas and 6 plexiform neurofibromas) and 20 NF2-related tumors (10 meningiomas and 10 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. RESULTS: PD-L1 expression was detected in all tumors, with highest expression levels observed in plexiform neurofibromas and schwannomas. PD-L1 positive tumor cells with >5% membranous staining were observed in 6/6 (100%) of plexiform neurofibromas, 9/11 (82%) of dermal neurofibromas, 7/10 (70%) of schwannomas, and 4/10 (40%) of meningiomas. Sparse to moderate presence of CD68, CD3, or CD8 positive tumor-infiltrating lymphocytes (TILs) was found in 37/37 (100%) of tumor specimens. However, expression of CD20 positive lymphocytes was limited to rare cells detectable in 4/37 (11%) of tumors. CONCLUSION: Our findings indicate that adaptive resistance to cell-mediated immunity plays a major role in the tumor immune environment of NF1 and NF2 associated tumors. Expression of PD-L1 on tumor cells and presence of TILs suggests that these tumors may be responsive to immune therapy with immune checkpoint inhibitors, which should be explored in clinical trials for NF patients.