Upregulated immuno-modulator PD-L1 in malignant peripheral nerve sheath tumors provides a potential biomarker and a therapeutic target

Abstract

Background Malignant peripheral nerve sheath tumors (MPNSTs) are rare aggressive sarcomas with poor prognosis. More than half of MPNSTs develop from benign precursor tumors associated with neurofibromatosis type 1 (NF1) which is a tumor suppressor gene disorder. Early detection of malignant transformation in NF1 patients is pivotal to improving survival. The primary aim of this study was to evaluate the role of immuno-modulators as candidate biomarkers of malignant transformation in NF1 patients with plexiform neurofibromas as well as predictors of response to immunotherapeutic approaches. Methods Sera from a total of 125 NF1 patients with quantified internal tumor load were included, and 25 of them had MPNSTs. A total of six immuno-modulatory factors (IGFBP-1, PD-L1, IFN-α, GM-CSF, PGE-2, and AXL) were measured in these sera using respective ELISA. Results NF1 patients with MPNSTs had significantly elevated PD-L1 levels in their sera compared to NF1 patients without MPNSTs. By contrast, AXL concentrations were significantly lower in sera of NF1-MPNST patients. IGFBP-1 and PGE2 serum levels did not differ between the two patient groups. IFN-α and GM-CSF were below the detectable level in most samples. Conclusion The immuno-modulator PD-L1 is upregulated in MPNST patients and therefore may provide as a potential biomarker of malignant transformation in patients with NF1 and as a response predictor for immunotherapeutic approaches.

Hydroxypropyl β-Cyclodextrin-Functionalized MoO3 Quantum Dots as a Multifunctional Probe for PGE2 Detection, Bioimaging, and Oxidative Stress Management in Inflammatory Diseases

“…The probe showed a similar intensity response with an excellent percentage recovery (Table S1) in the recovery range of 100 ± 3%, evidencing the applicability of the probe for real-time detection of PGE2. The observed detection capability of the MoCD QD probe is well-suitable for clinical diagnosis, which falls under the threshold level. , …”

“…The observed detection capability of the MoCD QD probe is well-suitable for clinical diagnosis, which falls under the threshold level. 18,19 The robustness of the synthesized MoCD QD fluorescence probe and its high selectivity and specificity with excellent realsample detection of PGE2 demonstrate the practicability in the diagnosis of PGE2-associated inflammatory conditions in real samples for point-of-care detection.…”

“…The COX-2/PGE2/EP axis contributes significantly to tumor progression and therapy resistance . PGE2 is a promising molecular target and potential prognostic biomarker for inflammation-related diseases, including cancer, enabling in vivo tumor detection. , , − Therefore, therapies targeting oxidative stress and inflammation are vital in managing various diseases including cancer and autoimmune disorders.…”

Metabolic Features of Neurofibromatosis Type 1-Associated Tumors

“…As for glioma, chemotherapy remains the first line treatment. More recently, epigenetic-based approaches in fighting MPNST growth have emerged [55] and drugs targeting the immune checkpoints are considered the emerging therapeutic option with ongoing clinical trials [56,57] (https://clinicaltrials.gov/ct2/show/ NCT02691026).…”

Immune system changes in the pathogenesis of neurofibromatosis type 1

“…Активация цитоки нов и онкогенных сигнальных путей PI3 / AktmTOR, тирозинкиназы EGFR и MEK приводит к стимуляции PDL1 [53]. У больных НФ1 с наличием MPNST опре деляются значительно более высокие уровни PDL1, что свидетельствует о потенциальной эффективности чекпойнтингибиторов для лечения этого агрессивно го типа опухоли [54]. Это подтверждается данными об эффективном применении в терапии плексиформ ных нейрофибром при НФ1 ингибиторов MEK, кото рые вызывают уменьшение размеров опухолей у 71-95 % больных НФ1 [55,56].…”