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PD‑1/PD‑L1 immune checkpoint in bone and soft tissue tumors (Review)
Kazuhiko Hashimoto1, Shunji Nishimura1, Koji Goto1
1Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama, Osaka 589-8511, Japan.
Abstract:
Anti-programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1) drugs have been used clinically, including those for skin cancer, with reasonable efficacy. Despite extensive ongoing research on bone and soft tissue sarcomas, there is a paucity of reviews that present a coherent picture. The present article is a comprehensive narrative review on the role of the PD-1/PD-L1 immune checkpoint in bone and soft tissue tumors. The review outlines the biological functions and mechanisms of action of PD-1/PD-L1 and its expression and clinical significance in various tumor types, including osteosarcoma and soft tissue sarcoma. Clinical trial results of immune checkpoint inhibitors, their association with prognosis, mechanisms of resistance to therapy, immune-related adverse events, and their potential in combination therapies, were also discussed.
Insights
Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) and PD-1 ligand-1 (PD-L1) show promise for bone and soft tissue sarcomas. This review details their mechanisms, clinical significance, and therapeutic potential in these rare cancers.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Anti-programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1) therapies are established for some cancers.
- Bone and soft tissue sarcomas lack comprehensive reviews on PD-1/PD-L1 immune checkpoint roles.
Purpose of the Study:
- To provide a comprehensive narrative review of the PD-1/PD-L1 immune checkpoint in bone and soft tissue tumors.
- To synthesize current knowledge on PD-1/PD-L1 biology, expression, and clinical relevance in these cancers.
Main Methods:
- Comprehensive literature search and narrative review methodology.
- Analysis of biological functions, mechanisms of action, and tumor expression of PD-1/PD-L1.
- Review of clinical trial data, prognostic associations, resistance mechanisms, and combination therapy potential.
Main Results:
- PD-1/PD-L1 pathway plays a role in immune evasion in various tumors, including osteosarcoma and soft tissue sarcoma.
- Clinical trials of immune checkpoint inhibitors (ICIs) in sarcomas are emerging, with variable efficacy.
- Understanding resistance mechanisms and immune-related adverse events is crucial for optimizing ICI therapy.
Conclusions:
- The PD-1/PD-L1 axis represents a potential therapeutic target in bone and soft tissue sarcomas.
- Further research is needed to elucidate ICI efficacy, resistance, and optimal combination strategies for these malignancies.
