PD-L1 Expression and Tumor Infiltrating Lymphocytes in Neurofibromatosis Type 1-Related Benign Tumors and Malignant Peripheral Nerve Sheath Tumors: An Implication for Immune Checkpoint Inhibition Therapy

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disorder. It can affect multiple systems of the body and cause severe disfigurement and discomfort in these patients. There are two types of neurofibromas, named cutaneous and plexiform neurofibromas. The latter type may transform into malignant peripheral nerve sheath tumors (MPNSTs). Surgical resection is difficult to perform owing to the complex tissue structure of neurofibromas; therefore, it is necessary to develop novel and effective therapies for the treatment of these tumors. Programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1)-related immune checkpoint inhibitors have been proven effective for various cancers, and the positive expression of PD-L1 and tumor-infiltrating lymphocytes (TILs) has been recognized as a biomarker for the response to immune checkpoint therapy. We conducted immunohistochemistry (IHC) staining to detect PD-L1 expression in plexiform neurofibroma and MPNST tissue samples. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were performed to detect PD-L1 and PD-1 expression in MPNST cell lines. IHC staining was used to show immune cell infiltration in NF1 and MPNST tissues. IHC staining showed PD-L1 positive expression in neurofibromas and MPNST tumor tissues. In addition, qPCR and western blotting showed high expression of PD-L1 in MPNST tumor cells. IHC staining revealed that aberrant T lymphocytes infiltrated the plexiform neurofibroma and MPNST tumor tissues. These results indicate that immune checkpoint mechanisms may play a pivotal role in the development of NF1-related tumors, and immune checkpoint inhibitors may be effective for managing neurofibromas and MPNSTs. Combined therapy with other molecular agents may be explored in the future.