{"doi":"10.3389/fimmu.2022.872353","title":"The Prognostic Value of Natural Killer Cells and Their Receptors/Ligands in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>Natural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Several electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57–0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57<jats:sup>+</jats:sup> NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56<jats:sup>+</jats:sup> NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>NK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.</jats:p></jats:sec>","journal":"Frontiers in Immunology","year":2022,"id":687994,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1797344,"name":"Zi-Niu Ding","orcid":null,"position":1,"is_corresponding":false},{"id":1797345,"name":"Guang-Xiao Meng","orcid":null,"position":2,"is_corresponding":false},{"id":1797346,"name":"Lun-Jie Yan","orcid":null,"position":3,"is_corresponding":false},{"id":1364923,"name":"Hui Liu","orcid":"0000-0003-0148-0125","position":4,"is_corresponding":false},{"id":1797347,"name":"Hai-Chao Li","orcid":null,"position":5,"is_corresponding":false},{"id":1797348,"name":"Sheng-Yu Yao","orcid":null,"position":6,"is_corresponding":false},{"id":1797349,"name":"Bao-Wen Tian","orcid":null,"position":7,"is_corresponding":false},{"id":1797350,"name":"Zhao-Ru Dong","orcid":null,"position":8,"is_corresponding":false},{"id":1675558,"name":"Zhi-Qiang Chen","orcid":null,"position":9,"is_corresponding":false},{"id":1664703,"name":"Jian-Guo Hong","orcid":null,"position":10,"is_corresponding":false},{"id":1797351,"name":"Dong-Xu Wang","orcid":null,"position":11,"is_corresponding":false},{"id":435652,"name":"Tao Li","orcid":"0000-0002-7988-3090","position":12,"is_corresponding":false},{"id":1797343,"name":"Jun-Shuai Xue","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Prognostic Value of Natural Killer Cells and Their Receptors/Ligands in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>Natural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Several electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57–0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57<jats:sup>+</jats:sup> NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56<jats:sup>+</jats:sup> NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>NK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":3.295836866004329,"endowment":3.295836866004329,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35464489","pmcid":"PMC9021421","openalex_id":"https://openalex.org/W4225356740","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"","title":null}],"total_grants":1,"fwci":1.8809,"citation_percentile":0.8336714,"influential_citations":0,"citation_trend":[{"year":2022,"count":2},{"year":2023,"count":6},{"year":2024,"count":4},{"year":2025,"count":10},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.3389/fimmu.2022.872353","host_type":"journal"},{"url":"https://doi.org/10.3389/fimmu.2022.872353","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2022.872353/full","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35464489","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9021421","host_type":"repository"},{"url":"https://doaj.org/article/358fdd875236470b85f6a61a1770c82c","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9021421","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9021421?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Immune Cell Function and Interaction","Cancer, Stress, Anesthesia, and Immune Response","Immune cells in cancer","Carcinoma, Hepatocellular","Humans","Killer Cells, Natural","Ligands","Liver Neoplasms","Prognosis","Prospective Studies"],"mesh_terms":["Carcinoma, Hepatocellular","Humans","Killer Cells, Natural","Ligands","Liver Neoplasms","Prognosis","Prospective Studies"],"keywords":["Hepatocellular carcinoma","Receptor","Cancer research","Medicine","Oncology","Biology","Internal medicine","Ligand","Prognosis","Natural killer cells"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-19T11:50:38.580523Z","pmid":null,"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":[]}