Key Immune Checkpoint PD-1/PD-L1 Signaling Pathway Components in the Blood Serum from Patients with Bone Tumors

Кушлинский, Н. Е.; Alferov, A.A.; Timofeev, Yu. S.; Es, Gershteĭn; Булычева, И. В.; Bondarev, A. V.; Shchupak, M Yu; Sokolov, N Yu; Поликарпова, С. Б.; Efimova, M M; Dzampaev, A A; Сушенцов, Е. А.; Алиев, М.Д.; Мусаев, Э. Р.

doi:10.1007/s10517-020-05005-2

Cited by 8 publications

(8 citation statements)

References 13 publications

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“…Positive PD-L1 expression on tumor cells is associated with advanced stages [ 28 ], and the density of PD-1+ tumor-infiltrating lymphocytes is associated with the invasion of surrounding muscles [ 29 , 30 ]. Comparative analysis reveals higher levels of soluble forms of PD-L1 in the blood serum of chordoma patients in comparison with healthy persons, but the soluble form of PD-1 is at the same level in both chordoma patients and healthy persons [ 31 ]. So, immunotherapy of PD-1/ L1 may be a potential therapy in advanced patients of chordoma.…”

Section: Discussionmentioning

confidence: 99%

Bibliometric analysis of the global research trends and hotspots in chordoma from 2000 to 2020

et al. 2022

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Introduction Chordoma is formed from embryonic residues or ectopic chordae and locally aggressive or malignant tumors. We visually analyzed the research tendency and hotspot of chordoma. Methods The bibliometric analysis was conducted from the Web of Science Core Collection database over the past two decades. The term and strategies were as follows: “TS = (chordoma) OR TS = (chordoblastoma) OR TS = (chordocarcinoma) OR TS = (chordoepithelioma) OR TS = (chordosarcoma) OR TS = (notochordoma). AND Language: English. AND Reference Type: Article OR Review”. A total of 2,118 references were retrieved and used to make a visual analysis by VOSviewer 1.6.15. Results The chordoma was on a steady rise and chordoma but remained the focus of scholars and organizations over the last two decades. The Chinese institutions and scholars lacked cooperation with their counterparts in other countries. The citations of documents and co-citation analysis of cited references suggested that M.L. McMaster, B.P. Walcott, P. Bergh, and S. Stacchiotti were leading researchers in this field of chordoma and their papers had been widely accepted and inspired recent researches. Keywords associated with recent chemotherapy, PD-1-related immunotherapy, and SMARCB1/integrase interactor 1 (INI1) in chordoma were a shortage of research and there may be more research ideas in the future by scholars. The research of chordoma will continue to be the hotspot. Conclusions Thus, explaining the molecular mechanism and potential role of transcriptional inhibition and immunologic responses to SMARCB1/INI1-negative poorly differentiated chordoma will be available for preclinical experiments and clinical trials and lead to new therapeutic opportunities for chordoma patients.

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Section: Discussionmentioning

confidence: 99%

Bibliometric analysis of the global research trends and hotspots in chordoma from 2000 to 2020

et al. 2022

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“…PD‐1 and PD‐L1 were found to be expressed in 47 and 53% of biopsy specimens, respectively, according to studies examining PD‐1, PD‐L1, and associated immunomarkers in samples of individuals with OS 138 . Additionally, a negative correlation exists between PD‐1/PD‐L1 overexpression and patient survival 139–142 . Consequently, PD‐1/PD‐L1 overexpression is a poor prognostic indicator for OS.…”

Section: Signaling Pathways In Osmentioning

confidence: 99%

“… 138 Additionally, a negative correlation exists between PD‐1/PD‐L1 overexpression and patient survival. 139 , 140 , 141 , 142 Consequently, PD‐1/PD‐L1 overexpression is a poor prognostic indicator for OS.…”

Section: Signaling Pathways In Osmentioning

confidence: 99%

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Shen

Lan

et al. 2023

MedComm

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Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant bone tumors. Neoadjuvant chemotherapy combined with limb‐preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases and OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management of OS. There has been an urgent need to identify new biomarkers for OS to develop specific targeted therapies. Recently, the continued advancements in genomic analysis have contributed to the identification of clinically significant molecular biomarkers for diagnosing OS, acting as therapeutic targets, and predicting prognosis. Additionally, the contemporary molecular classifications have revealed that the signaling pathways, including Wnt/β‐catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD‐1/PD‐L1, MAPK, and NF‐κB, have an integral role in OS onset, progression, metastasis, and treatment response. These molecular classifications and biological markers have created new avenues for more accurate OS diagnosis and relevant treatment. We herein present a review of the recent findings for the modulatory role of signaling pathways as possible biological markers and treatment targets for OS. This review also discusses current OS therapeutic approaches, including signaling pathway‐based therapies developed over the past decade. Additionally, the review covers the signaling targets involved in the curative effects of traditional Chinese medicines in the context of expression regulation of relevant genes and proteins through the signaling pathways to inhibit OS cell growth. These findings are expected to provide directions for integrating genomic, molecular, and clinical profiles to enhance OS diagnosis and treatment.

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“…Another potential therapeutic target recently identified in GCTB is the PD-1/PD-L1 immune checkpoint. Kushlinskii et al studied levels of sPD-1/sPD-L1 in blood serum samples of GCTB patients, patients with other bone tumors and healthy controls, and found higher sPD-L1 levels in all patients with bone neoplasms compared with controls, and higher sPD-1 levels in patients with GCTB and osteosarcoma compared with controls, benign neoplasms, chondrosarcoma, and chordoma [19 ▪▪ ]. Metovic et al studied immunohistochemical PD-L1 expression in 46 GCTB and 24 aneurysmal bone cysts (ABC) and found PD-L1 expression in 28% of GCTB and 4% in ABC [20 ▪▪ ].…”

Section: Diagnostics and Translational Researchmentioning

confidence: 99%

Updated concepts in treatment of giant cell tumor of bone

Heijden¹,

Lipplaa²,

Langevelde³

et al. 2022

Current Opinion in Oncology

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Purpose of reviewGiant cell tumors of bone (GCTB) are intermediate, locally aggressive primary bone tumors. For conventional GCTB, surgery remains treatment of choice. For advanced GCTB, a more important role came into play for systemic therapy including denosumab and bisphosphonates over the last decade.Recent findingsIn diagnostics, focus has been on H3F3A (G34) driver mutations present in GCTB. The most frequent mutation (G34W) can be detected using immunohistochemistry and is highly specific in differentiating GCTB from other giant cell containing tumors. PD-L1 expression can be used as biological marker to predict higher recurrence risks in GCTB patients.The use of bisphosphonate-loaded bone cement is under investigation in a randomized controlled trial. A new technique consisting of percutaneous microwave ablation and bisphosphonate-loaded polymethylmethacrylate cementoplasty was proposed for unresectable (pelvic) GCTB.Increased experience with use of denosumab raised concern on elevated recurrence rates. However, conclusions of meta-analyses should be interpreted with risk of indication bias in mind. Several small studies are published with short-course denosumab (varying from 3 to 6 doses). One small trial directly compared denosumab and zoledronic acid, with no statistical differences in radiological and clinical outcome, and nonsignificantly higher recurrence rate after denosumab. As bisphosphonates directly target neoplastic stromal cells in GCTB, larger directly comparative trials are still warranted.SummaryNeoadjuvant denosumab is highly effective for advanced GCTB, and a short-course is advised to facilitate surgery, whereas increased recurrence rates remain of concern. Randomized controlled trials are conducted on bisphosphonate-loaded bone cement and on optimal dose and duration of neoadjuvant denosumab. PD-L1 could be a potential new therapy target in GCTB.

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Key Immune Checkpoint PD-1/PD-L1 Signaling Pathway Components in the Blood Serum from Patients with Bone Tumors

Cited by 8 publications

References 13 publications

Bibliometric analysis of the global research trends and hotspots in chordoma from 2000 to 2020

Bibliometric analysis of the global research trends and hotspots in chordoma from 2000 to 2020

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Updated concepts in treatment of giant cell tumor of bone

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