{"doi":"10.1172/jci133334","title":"PD-1 blockade inhibits osteoclast formation and murine bone cancer pain","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.","journal":"Journal of Clinical Investigation","year":2020,"id":50727,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":181,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":250586,"name":"Yun Gu","orcid":"0000-0001-6942-0749","position":1,"is_corresponding":false},{"id":250587,"name":"Yihan Liao","orcid":"0000-0002-2622-9036","position":2,"is_corresponding":false},{"id":250588,"name":"Sangsu Bang","orcid":"0000-0002-9092-0075","position":3,"is_corresponding":false},{"id":233677,"name":"Christopher R. Donnelly","orcid":"0000-0003-2487-8881","position":4,"is_corresponding":false},{"id":49828,"name":"Chen Ouyang","orcid":"0000-0003-1387-9408","position":5,"is_corresponding":false},{"id":250589,"name":"Xueshu Tao","orcid":"0000-0001-9667-9617","position":6,"is_corresponding":false},{"id":250590,"name":"Anthony J. Mirando","orcid":"0000-0001-9536-5528","position":7,"is_corresponding":false},{"id":250591,"name":"Matthew J. Hilton","orcid":"0000-0003-3165-267X","position":8,"is_corresponding":false},{"id":233682,"name":"Ru‐Rong Ji","orcid":"0000-0002-9355-3688","position":9,"is_corresponding":false},{"id":233680,"name":"Kaiyuan Wang","orcid":"0000-0002-8374-6427","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T20:39:29.006085Z","pmid":"32484460","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}