Digging Through the Complexities of Immunological Approaches in Emerging Osteosarcoma Therapeutics: A Comprehensive Narrative Review with Updated Clinical Trials

Osteosarcoma (OS) is the predominant mesenchymal primary malignant bone tumor in oncology and pathology, impacting a wide age range from adolescents to older adults. It frequently advances to lung metastasis, ultimately resulting in the mortality of OS patients. The precise pathological pathways res...

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Published inBiomedicines Vol. 13; no. 3; p. 664
Main Authors Sergi, Consolato M., Burnett, Mervin, Jantuan, Eugeniu, Hakoum, Mariam, Beug, Shawn T., Leng, Roger, Shen, Fan
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 08.03.2025
MDPI
Subjects
Angiogenesis
Bispecific antibodies
bone
Bone cancer
Bone tumors
Cancer
Cancer therapies
Care and treatment
Chemotherapy
Chimeric antigen receptors
Clinical trials
Cytokines
Drug therapy
Enzymes
Genotype & phenotype
Immune checkpoint inhibitors
Immune system
Immunogenicity
Immunology
Immunomodulators
Immunotherapy
Lymphocytes T
Macrophages
Medical innovations
Medical prognosis
Metastases
Metastasis
Microenvironments
Natural killer cells
Nitric oxide
Omics
Osteosarcoma
Patients
Phosphorylation
Physiological aspects
Review
therapy
Tumors
Canada
bone
Osteosarcoma
immunology
therapy
Omics
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Abstract Osteosarcoma (OS) is the predominant mesenchymal primary malignant bone tumor in oncology and pathology, impacting a wide age range from adolescents to older adults. It frequently advances to lung metastasis, ultimately resulting in the mortality of OS patients. The precise pathological pathways responsible for OS progression and dissemination are not fully understood due to its heterogeneity. The integration of surgery with neoadjuvant and postoperative chemotherapy has significantly increased the 5-year survival rate to more than 70% for patients with localized OS tumors. However, about 30% of patients experience local recurrence and/or metastasis. Hence, there is a requirement for innovative therapeutic approaches to address the limitations of traditional treatments. Immunotherapy has garnered increasing attention as a promising avenue for tumors resistant to standard therapies, including OS, despite the underlying mechanisms of disease progression and dissemination remaining not well elucidated. Immunotherapy may not have been suitable for use in patients with OS because of the tumor’s immunosuppressive microenvironment and limited immunogenicity. Nevertheless, there are immune-based treatments now being developed for clinical use, such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors. Also, additional immunotherapy techniques including cytokines, vaccines, and modified-Natural Killer (NK) cells/macrophages are in the early phases of research but will certainly be popular subjects in the nearest future. Our goal in writing this review was to spark new lines of inquiry into OS immunotherapy by summarizing the findings from both preclinical and current clinical studies examining different approaches.
AbstractList Osteosarcoma (OS) is the predominant mesenchymal primary malignant bone tumor in oncology and pathology, impacting a wide age range from adolescents to older adults. It frequently advances to lung metastasis, ultimately resulting in the mortality of OS patients. The precise pathological pathways responsible for OS progression and dissemination are not fully understood due to its heterogeneity. The integration of surgery with neoadjuvant and postoperative chemotherapy has significantly increased the 5-year survival rate to more than 70% for patients with localized OS tumors. However, about 30% of patients experience local recurrence and/or metastasis. Hence, there is a requirement for innovative therapeutic approaches to address the limitations of traditional treatments. Immunotherapy has garnered increasing attention as a promising avenue for tumors resistant to standard therapies, including OS, despite the underlying mechanisms of disease progression and dissemination remaining not well elucidated. Immunotherapy may not have been suitable for use in patients with OS because of the tumor’s immunosuppressive microenvironment and limited immunogenicity. Nevertheless, there are immune-based treatments now being developed for clinical use, such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors. Also, additional immunotherapy techniques including cytokines, vaccines, and modified-Natural Killer (NK) cells/macrophages are in the early phases of research but will certainly be popular subjects in the nearest future. Our goal in writing this review was to spark new lines of inquiry into OS immunotherapy by summarizing the findings from both preclinical and current clinical studies examining different approaches.
Osteosarcoma (OS) is the predominant mesenchymal primary malignant bone tumor in oncology and pathology, impacting a wide age range from adolescents to older adults. It frequently advances to lung metastasis, ultimately resulting in the mortality of OS patients. The precise pathological pathways responsible for OS progression and dissemination are not fully understood due to its heterogeneity. The integration of surgery with neoadjuvant and postoperative chemotherapy has significantly increased the 5-year survival rate to more than 70% for patients with localized OS tumors. However, about 30% of patients experience local recurrence and/or metastasis. Hence, there is a requirement for innovative therapeutic approaches to address the limitations of traditional treatments. Immunotherapy has garnered increasing attention as a promising avenue for tumors resistant to standard therapies, including OS, despite the underlying mechanisms of disease progression and dissemination remaining not well elucidated. Immunotherapy may not have been suitable for use in patients with OS because of the tumor's immunosuppressive microenvironment and limited immunogenicity. Nevertheless, there are immune-based treatments now being developed for clinical use, such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors. Also, additional immunotherapy techniques including cytokines, vaccines, and modified-Natural Killer (NK) cells/macrophages are in the early phases of research but will certainly be popular subjects in the nearest future. Our goal in writing this review was to spark new lines of inquiry into OS immunotherapy by summarizing the findings from both preclinical and current clinical studies examining different approaches.Osteosarcoma (OS) is the predominant mesenchymal primary malignant bone tumor in oncology and pathology, impacting a wide age range from adolescents to older adults. It frequently advances to lung metastasis, ultimately resulting in the mortality of OS patients. The precise pathological pathways responsible for OS progression and dissemination are not fully understood due to its heterogeneity. The integration of surgery with neoadjuvant and postoperative chemotherapy has significantly increased the 5-year survival rate to more than 70% for patients with localized OS tumors. However, about 30% of patients experience local recurrence and/or metastasis. Hence, there is a requirement for innovative therapeutic approaches to address the limitations of traditional treatments. Immunotherapy has garnered increasing attention as a promising avenue for tumors resistant to standard therapies, including OS, despite the underlying mechanisms of disease progression and dissemination remaining not well elucidated. Immunotherapy may not have been suitable for use in patients with OS because of the tumor's immunosuppressive microenvironment and limited immunogenicity. Nevertheless, there are immune-based treatments now being developed for clinical use, such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors. Also, additional immunotherapy techniques including cytokines, vaccines, and modified-Natural Killer (NK) cells/macrophages are in the early phases of research but will certainly be popular subjects in the nearest future. Our goal in writing this review was to spark new lines of inquiry into OS immunotherapy by summarizing the findings from both preclinical and current clinical studies examining different approaches.
Audience Academic
Author Hakoum, Mariam
Beug, Shawn T.
Shen, Fan
Leng, Roger
Sergi, Consolato M.
Jantuan, Eugeniu
Burnett, Mervin
AuthorAffiliation 3 CHEO Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada; mhako096@uottawa.ca (M.H.)
1 Division of Anatomic Pathology, Department of Laboratory Medicine, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada
2 Department of Laboratory Medicine, Stollery Children’s Hospital, University of Alberta, Edmonton, AB T6G 2R3, Canada jant.eugen@yahoo.com (E.J.); fanshen2020@gmail.com (F.S.)
AuthorAffiliation_xml – name: 1 Division of Anatomic Pathology, Department of Laboratory Medicine, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada
– name: 2 Department of Laboratory Medicine, Stollery Children’s Hospital, University of Alberta, Edmonton, AB T6G 2R3, Canada jant.eugen@yahoo.com (E.J.); fanshen2020@gmail.com (F.S.)
– name: 3 CHEO Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada; mhako096@uottawa.ca (M.H.)
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  givenname: Consolato M.
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  surname: Sergi
  fullname: Sergi, Consolato M.
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  surname: Burnett
  fullname: Burnett, Mervin
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  givenname: Eugeniu
  orcidid: 0000-0002-4645-3617
  surname: Jantuan
  fullname: Jantuan, Eugeniu
– sequence: 4
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  surname: Beug
  fullname: Beug, Shawn T.
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  orcidid: 0000-0001-7432-8891
  surname: Shen
  fullname: Shen, Fan
BackLink https://www.ncbi.nlm.nih.gov/pubmed/40149640$$D View this record in MEDLINE/PubMed
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Keywords bone
Osteosarcoma
immunology
therapy
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Snippet Osteosarcoma (OS) is the predominant mesenchymal primary malignant bone tumor in oncology and pathology, impacting a wide age range from adolescents to older...
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SubjectTerms Angiogenesis
Bispecific antibodies
bone
Bone cancer
Bone tumors
Cancer
Cancer therapies
Care and treatment
Chemotherapy
Chimeric antigen receptors
Clinical trials
Cytokines
Drug therapy
Enzymes
Genotype & phenotype
Immune checkpoint inhibitors
Immune system
Immunogenicity
Immunology
Immunomodulators
Immunotherapy
Lymphocytes T
Macrophages
Medical innovations
Medical prognosis
Metastases
Metastasis
Microenvironments
Natural killer cells
Nitric oxide
Omics
Osteosarcoma
Patients
Phosphorylation
Physiological aspects
Review
therapy
Tumors
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Title Digging Through the Complexities of Immunological Approaches in Emerging Osteosarcoma Therapeutics: A Comprehensive Narrative Review with Updated Clinical Trials
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Volume 13
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