Abstract
BackgroundRhabdomyosarcomas (RMSs) are the most frequent soft tissue sarcoma in children and adolescents, defined by skeletal muscle differentiation and the status of FOXO1 fusions. In pediatric malignancies, in particular RMS, scant and controversial observations are reported about PD-L1 expression as a putative biomarker and few immune checkpoint clinical trials are conducted.MethodsPD-L1 assessment was evaluated by immunohistochemistry (IHC) utilizing two anti-PDL1 antibodies, in a pilot cohort of 25 RMS. Results were confirmed in primary and commercial RMS cell lines by cytofluorimetric analysis and IHC.ResultsPD-L1 expression was detectable, by both anti-PD-L1 antibodies, in the immune contexture of immune cells infiltrating and/or surrounding the tumor, in 15/25 (60%) RMS, while absent expression was observed in neoplastic cells. Flow cytometry analysis and PD-L1 IHC of commercial and primary RMS cell lines confirmed a very small percentage of PD-L1 positive-tumor cells, under the detection limits of conventional IHC. Interestingly, increased PD-L1 expression was observed in the immune contexture of 4 RMS cases post chemotherapy compared to their matched pre-treatment samples.ConclusionHere we identify a peculiar pattern of PD-L1 expression in our RMS series with scanty positive-tumor cells detected by flow cytometry, and recurrent expression in the immune cells surrounding or infiltrating the tumor burden.
Highlights
Rhabdomyosarcomas (RMSs) are the most frequent soft tissue sarcoma in children and adolescents, defined by skeletal muscle differentiation and the status of FOXO1 fusions
Interpretation of PD-L1 expression by immunohistochemistry For both antibodies, PD-L1 staining was evaluated in tumor cells (TC) and in non-neoplastic cells enclosed in stromal microenvironment, named tumor infiltrating cells (IC) by two experienced pathologists (SLR, PC, MB)
Two different anti PD-L1 antibodies were utilized and for both PD-L1 staining was evaluated and scored in tumor cells (TC) and in non-neoplastic cells enclosed in stromal microenvironment, named tumor infiltrating cells (IC) for each RMS specimen (Table 1)
Summary
Rhabdomyosarcomas (RMSs) are the most frequent soft tissue sarcoma in children and adolescents, defined by skeletal muscle differentiation and the status of FOXO1 fusions. Rhabdomyosarcoma (RMS) is a highly aggressive tumor arising from immature mesenchymal cells committed to skeletal muscle differentiation, it represents the most frequent soft tissue sarcoma in childhood. It is generally responsive to the multimodal therapeutic approaches including intensive chemotherapy, the prognosis of RMS depends on several different variables and for some patients the outcome remains dismal [1]. Pediatric RMS has two major histological subtypes, each with distinct clinical, molecular, and genetic features: the embryonal RMS (ERMS) are more frequent (~ 80% of cases) with a higher incidence in younger children; and the alveolar RMS (ARMS), less frequent (~ 20% of cases) but more aggressive and often resistant to conventional chemo- and radiotherapy, resulting in a 5-year survival rate of only 30% [2,3,4,5]. The identification and development of more efficient and less toxic therapeutic approaches is absolutely needed [7]
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