ArticleThe Journal of clinical investigation2020
PD-1 blockade inhibits osteoclast formation and murine bone cancer pain.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
132 citing papers in PubMed, 3 syntheses or guidelines pooled it, 175 citations in OpenAlex.
- The effect of radiotherapy, chemotherapy, and immunotherapy on fusion rate in spinal surgery using osteobiologics for patients with metastatic spinal disease: a systematic review.Neurosurgical review · 2024Pooled it
- Impact of bone metastasis on prognosis in non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Bibliometric analysis of bone metastases from lung cancer research from 2004 to 2023.Frontiers in oncology · 2024Pooled it
- Protocol for a cohort study: evaluating the effect of neoadjuvant immunochemotherapy on intraoperative remifentanil consumption during IoC2-guided anesthesia in elderly patients with esophageal cancer.Annals of medicine · 2026Observational
- Bioactive polythioctic acid-engineered ropivacaine alleviates bone cancer pain through prolonged analgesia and multi-functional neuroprotection.Materials today. Bio · 2026Article
- Tumor-derived CTHRC1 mediates ITGB3-dependent osteoclast differentiation to promote prostate cancer bone metastasis.Oncogene · 2026Article
- Cancer-related pain: A bidirectional modulator of cancer progression.Clinical and translational medicine · 2026Review
- Myeloid cell reprogramming combined with zoledronic acid effectively suppresses bone metastasis.Cancer biology & medicine · 2026Article
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Expansion of bone marrow adipocytes in obese mice leads to PD-L1-driven bone marrow immunosuppression and osteoclastogenesis.Bone research · 2026Article
- Tetrahydropalmatine alleviates cancer induced bone pain by inhibiting TRPV1-SP-mediated macrophage recruitment and promoting M2 polarization.Chinese medicine · 2026Article
- Multifunctional nanoplatforms deciphering immune resistance in bone tumors: cooperative delivery, immune reprogramming and microenvironment remodeling.Journal of nanobiotechnology · 2026Review
- Immune Checkpoint Inhibitors and Bone Health: Mechanisms, Clinical Implications, and Emerging Perspectives on Bone Fragility.Current osteoporosis reports · 2026Review
- Bibliometric analysis of bone metastasis from prostate cancer research from 2007 to 2024.Discover oncology · 2026Article
- Bone Adverse Events in Cancer Patients Undergoing Immune Checkpoint Inhibitor Therapy: A Comprehensive Review of the Literature from the Clinical Action Group of the European Calcified Tissue Society.Calcified tissue international · 2026Review
- Breaking Through Cancer Pain: From Single-Drug Management to Multimodal Analgesia.Pain research & management · 2026Review
- Mechanism of BMSCs Inhibiting Microglia Activation and Neuroinflammatory Response to Alleviate BCP by Regulating TLR4/ NF-κB Signaling Pathway.Journal of inflammation research · 2026Article
- M2 macrophage-secreted exosomal miR-216a regulates microglial polarization by targeting the HMGB1/TLR4/NF-κB pathway to alleviate bone cancer pain.American journal of translational research · 2026Article
- Targeting Inflammatory Cell Death: A Strategy for Discogenic Pain Relief.Journal of pain research · 2026Review
72 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Emerging immune therapy, such as with the anti-programmed cell death-1 (anti-PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with terminal cancer suffer from cancer pain as a result of bone metastasis and bone destruction, but how PD-1 blockade affects bone cancer pain remains unknown. Here, we report that mice lacking Pdcd1 (Pd1-/-) demonstrated remarkable protection against bone destruction induced by femoral inoculation of Lewis lung cancer cells. Compared with WT mice, Pd1-/- mice exhibited increased baseline pain sensitivity, but the development of bone cancer pain was compromised in Pd1-/- mice. Consistently, these beneficial effects in Pd1-/- mice were recapitulated by repeated i.v. applications of nivolumab in WT mice, even though nivolumab initially increased mechanical and thermal pain. Notably, PD-1 deficiency or nivolumab treatment inhibited osteoclastogenesis without altering tumor burden. PD-L1 and CCL2 are upregulated within the local tumor microenvironment, and PD-L1 promoted RANKL-induced osteoclastogenesis through JNK activation and CCL2 secretion. Bone cancer upregulated CCR2 in primary sensory neurons, and CCR2 antagonism effectively reduced bone cancer pain. Our findings suggest that, despite a transient increase in pain sensitivity following each treatment, anti-PD-1 immunotherapy could produce long-term benefits in preventing bone destruction and alleviating bone cancer pain by suppressing osteoclastogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.