PD-L1 and PU.1 expression in malignant peripheral nerve sheath tumors

Introduction. Malignant peripheral nerve sheath tumors (MPNSTs) belong to a rare heterogeneous group of aggressive neoplasms of mesenchymal origin. The relationship between the PD-L1 expression and development and prognosis of MPNSTs has not yet been determined. In addition, it is yet to explore the role of tumor microenvironment, in particular tumor-associated macrophages, in solid tumors. The aim of the study was to determine the relationship between (1) PD-L1 expression and the nuclear marker of PU.1 expression in stromal cells and (2) overall survival (OS) and recurrence-free survival (RFS) in patients with MPNSTs. Materials and methods. The retrospective study included 46 adult patients with MPNSTs who underwent surgical or combined treatment from 1998 to 2021 at the N.N. Blokhin Oncology Research Center. We analyzed clinical and morphological parameters as well as the outcomes of surgical treatment. Immunohistochemistry was used to detect the expression of PD-L1, PU.1, and Ki-67. Results. We found positive PD-L1 staining in 28% of cases. PU.1 expression was observed in all samples. We showed a statistically significant correlation between PU.1 and PD-L1 expression levels. At a median follow-up of 37 months, PD-L1 positive status was associated with a lower median OS and RFS in the group of patients with grade III tumors (p=0.0003 and p=0.004, respectively). The median OS for tumors with high and low number of PU.1+ cells was 21 and 78 months, respectively (p<0.0001). Conclusion. To the best of our knowledge, this is the first study to describe the prognostic value of the macrophage marker PU.1 in patients with MPNST. High levels of PU.1+ cells, regardless of the tumor grade, and PD-L1 expression >1% of tumor cells in the patients with poorly-differentiated MPNSTs, produced a negative effect on OS and RFS. The analyzed expression of these markers can be used in prognostic tests and developing novel therapeutic treatment options. Keywords: malignant peripheral nerve sheath tumor, PD-L1 immunohistochemistry, PU.1, surgical treatment