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Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy

OBJECTIVES: The fact that studies on anti‐programmed cell death 1 (PD‐1) or its relevant ligand 1 (PD‐L1) have yielded such few responses greatly decreases the confidence in immunotherapy with checkpoint inhibitors for advanced osteosarcoma. We intended to characterize the expression of various chec...

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Autores principales: Xie, Lu, Chen, Chenglong, Liang, Xin, Xu, Jie, Sun, Xin, Sun, Kunkun, Yang, Rongli, Tang, Xiaodong, Guo, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977595/
https://www.ncbi.nlm.nih.gov/pubmed/36519392
http://dx.doi.org/10.1111/os.13620
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author Xie, Lu
Chen, Chenglong
Liang, Xin
Xu, Jie
Sun, Xin
Sun, Kunkun
Yang, Rongli
Tang, Xiaodong
Guo, Wei
author_facet Xie, Lu
Chen, Chenglong
Liang, Xin
Xu, Jie
Sun, Xin
Sun, Kunkun
Yang, Rongli
Tang, Xiaodong
Guo, Wei
author_sort Xie, Lu
collection PubMed
description OBJECTIVES: The fact that studies on anti‐programmed cell death 1 (PD‐1) or its relevant ligand 1 (PD‐L1) have yielded such few responses greatly decreases the confidence in immunotherapy with checkpoint inhibitors for advanced osteosarcoma. We intended to characterize the expression of various checkpoint molecules with immunohistochemistry in osteosarcoma specimens and analyzed the relationship of the expression of these checkpoint molecules with patients' clinical courses. METHODS: This study was a retrospective non‐intervention study from August 1st 2017 to March 1st 2020. Immunohistochemistry for B7‐H3 (CD276, Cluster of Differentiation 276), CD47 (Cluster of Differentiation 47), PD‐L1 (programmed cell death ligand 1), TIM3 (mucin‐domain containing‐3), TGF‐β (TransformingGrowth Factor β), CXCR 4 (Chemokine Receptor 4), CD27 (Cluster of Differentiation 27), IDO1 (Indoleamine 2,3‐dioxygenase 1), KIRs (Killer cell Immunoglobulin‐like Receptors), and SDF‐1 (Stromal cell‐Derived Factor‐1) was performed on 35 resected osteosarcoma specimens. Patients progressed upon first‐line chemotherapy with evaluable lesions were qualified for this study, and their specimens previously stored in the pathological department repository would be retrieved for analysis. Associations between the immunohischemistry markers and clinicopathological variables and survival were evaluated by the χ(2) displayed by cross‐table, Cox proportional hazards regression model, and Kaplan–Meier plots. RESULTS: The positive rates of B7‐H3, CD47, PD‐L1, TIM3, and TGF‐β expression in this sample of 35 heavily treated osteosarcomas were 29% (10/35), 15% (5/35), 9% (3/35), 6% (2/35), and 6% (2/35), respectively, and diverse staining intensities were observed. Among these advanced patients, 15/35 (43%) had positive checkpoint expression, of which 33% (5/15) showed evidence of the co‐expression of more than one checkpoint molecule. We did not find any obvious correlation with clinicopathological characteristics and the positive expression of these molecules. CONCLUSIONS: The present study highlights that only a small subset of progressive osteosarcomas, which had been heavily‐treated, expressed tumor immune‐associated checkpoint molecules, of which B7‐H3 was the most positively expressed checkpoint and might be a promising target for further osteosarcoma investigation.
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spelling pubmed-99775952023-03-02 Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy Xie, Lu Chen, Chenglong Liang, Xin Xu, Jie Sun, Xin Sun, Kunkun Yang, Rongli Tang, Xiaodong Guo, Wei Orthop Surg Research Articles OBJECTIVES: The fact that studies on anti‐programmed cell death 1 (PD‐1) or its relevant ligand 1 (PD‐L1) have yielded such few responses greatly decreases the confidence in immunotherapy with checkpoint inhibitors for advanced osteosarcoma. We intended to characterize the expression of various checkpoint molecules with immunohistochemistry in osteosarcoma specimens and analyzed the relationship of the expression of these checkpoint molecules with patients' clinical courses. METHODS: This study was a retrospective non‐intervention study from August 1st 2017 to March 1st 2020. Immunohistochemistry for B7‐H3 (CD276, Cluster of Differentiation 276), CD47 (Cluster of Differentiation 47), PD‐L1 (programmed cell death ligand 1), TIM3 (mucin‐domain containing‐3), TGF‐β (TransformingGrowth Factor β), CXCR 4 (Chemokine Receptor 4), CD27 (Cluster of Differentiation 27), IDO1 (Indoleamine 2,3‐dioxygenase 1), KIRs (Killer cell Immunoglobulin‐like Receptors), and SDF‐1 (Stromal cell‐Derived Factor‐1) was performed on 35 resected osteosarcoma specimens. Patients progressed upon first‐line chemotherapy with evaluable lesions were qualified for this study, and their specimens previously stored in the pathological department repository would be retrieved for analysis. Associations between the immunohischemistry markers and clinicopathological variables and survival were evaluated by the χ(2) displayed by cross‐table, Cox proportional hazards regression model, and Kaplan–Meier plots. RESULTS: The positive rates of B7‐H3, CD47, PD‐L1, TIM3, and TGF‐β expression in this sample of 35 heavily treated osteosarcomas were 29% (10/35), 15% (5/35), 9% (3/35), 6% (2/35), and 6% (2/35), respectively, and diverse staining intensities were observed. Among these advanced patients, 15/35 (43%) had positive checkpoint expression, of which 33% (5/15) showed evidence of the co‐expression of more than one checkpoint molecule. We did not find any obvious correlation with clinicopathological characteristics and the positive expression of these molecules. CONCLUSIONS: The present study highlights that only a small subset of progressive osteosarcomas, which had been heavily‐treated, expressed tumor immune‐associated checkpoint molecules, of which B7‐H3 was the most positively expressed checkpoint and might be a promising target for further osteosarcoma investigation. John Wiley & Sons Australia, Ltd 2022-12-15 /pmc/articles/PMC9977595/ /pubmed/36519392 http://dx.doi.org/10.1111/os.13620 Text en © 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Xie, Lu
Chen, Chenglong
Liang, Xin
Xu, Jie
Sun, Xin
Sun, Kunkun
Yang, Rongli
Tang, Xiaodong
Guo, Wei
Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy
title Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy
title_full Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy
title_fullStr Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy
title_full_unstemmed Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy
title_short Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy
title_sort expression and clinical significance of various checkpoint molecules in advanced osteosarcoma: possibilities for novel immunotherapy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977595/
https://www.ncbi.nlm.nih.gov/pubmed/36519392
http://dx.doi.org/10.1111/os.13620
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