{"doi":"10.3390/ijms22179168","title":"MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models","abstract":"<jats:p>The transcription factor CEBPA is a master regulator of liver homeostasis, myeloid cell differentiation and is downregulated in several oncogenic diseases. MTL-CEBPA is a small activating RNA drug which upregulates gene expression of CEBPA for treatment of hepatocellular carcinoma (HCC). We investigate whether MTL-CEBPA has immune modulatory effects by combining MTL-CEBPA with an anti-PD-1 checkpoint inhibitor (CPI) and/or radiofrequency ablation (RFA) in two preclinical models. First, mice with two flanks of HCC tumors (BNL) were treated with combinations of RFA (right flank), anti-PD-1 or MTL-CEBPA. The reduction of the left flank tumors was most pronounced in the group treated with RFA+anti-PD1+MTL-CEBPA and 7/8 animals responded. This was the only group with a significant increase in CD8+ and CD49b+/CD45+ tumor infiltrating lymphocytes (TIL). Second, a combination of anti-PD-1+MTL-CEBPA was tested in a CT26 colon cancer model and this treatment significantly reduced tumor size, modulated the tumor immune microenvironment and increased TILs. These data suggest a clinical role for combination treatment with CPIs, RFA and MTL-CEBPA through synergistic priming of the immune tumor response, enabling RFA and CPIs to have a pronounced anti-tumor effect including activity in non-treated tumors in the case of RFA.</jats:p>","journal":"International Journal of Molecular Sciences","year":2021,"id":651476,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"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":1699078,"name":"Choon Ping Tan","orcid":null,"position":1,"is_corresponding":false},{"id":639040,"name":"Vikash Reebye","orcid":"0000-0003-0811-5323","position":2,"is_corresponding":false},{"id":639046,"name":"Cheng Ean Chee","orcid":"0000-0003-2385-7712","position":3,"is_corresponding":false},{"id":1699079,"name":"Dimitris Zacharoulis","orcid":null,"position":4,"is_corresponding":false},{"id":389334,"name":"Robert Habib","orcid":null,"position":5,"is_corresponding":false},{"id":1699080,"name":"David C. Blakey","orcid":null,"position":6,"is_corresponding":false},{"id":111888,"name":"John J. Rossi","orcid":null,"position":7,"is_corresponding":false},{"id":639053,"name":"Nagy Habib","orcid":"0000-0003-4920-4154","position":8,"is_corresponding":false},{"id":639042,"name":"Mikael H. Sodergren","orcid":"0000-0002-7141-3924","position":9,"is_corresponding":false},{"id":639044,"name":"Kai‐Wen Huang","orcid":"0000-0001-6375-8714","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models","abstract":"<jats:p>The transcription factor CEBPA is a master regulator of liver homeostasis, myeloid cell differentiation and is downregulated in several oncogenic diseases. MTL-CEBPA is a small activating RNA drug which upregulates gene expression of CEBPA for treatment of hepatocellular carcinoma (HCC). We investigate whether MTL-CEBPA has immune modulatory effects by combining MTL-CEBPA with an anti-PD-1 checkpoint inhibitor (CPI) and/or radiofrequency ablation (RFA) in two preclinical models. First, mice with two flanks of HCC tumors (BNL) were treated with combinations of RFA (right flank), anti-PD-1 or MTL-CEBPA. The reduction of the left flank tumors was most pronounced in the group treated with RFA+anti-PD1+MTL-CEBPA and 7/8 animals responded. This was the only group with a significant increase in CD8+ and CD49b+/CD45+ tumor infiltrating lymphocytes (TIL). Second, a combination of anti-PD-1+MTL-CEBPA was tested in a CT26 colon cancer model and this treatment significantly reduced tumor size, modulated the tumor immune microenvironment and increased TILs. These data suggest a clinical role for combination treatment with CPIs, RFA and MTL-CEBPA through synergistic priming of the immune tumor response, enabling RFA and CPIs to have a pronounced anti-tumor effect including activity in non-treated tumors in the case of RFA.</jats:p>","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34502076","pmcid":"PMC8431011","openalex_id":"https://openalex.org/W3193520866","authors":[],"funders":[{"funder_name":"Ministry of Science and Technology, Taiwan","grant_id":"105-2314-B-002-059-MY3","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI161075","title":null}],"total_grants":2,"fwci":1.1355,"citation_percentile":0.81224447,"influential_citations":0,"citation_trend":[{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":4},{"year":2023,"count":5},{"year":2024,"count":4},{"year":2025,"count":6}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/22/17/9168/pdf?version=1629887594","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/22/17/9168/pdf?version=1629887594","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/22/17/9168/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms22179168","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34502076","host_type":"repository"},{"url":"https://doaj.org/article/46dd48525e454c118a6901a4a37277d2","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms22179168","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8431011","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8431011","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8431011?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer Immunotherapy and Biomarkers","Immune Cell Function and Interaction","Hepatocellular Carcinoma Treatment and Prognosis"],"mesh_terms":["Radiofrequency Ablation","Immune Checkpoint Inhibitors","Animals","Cells, Cultured","Colonic Neoplasms","Carcinoma, Hepatocellular","Liver Neoplasms","Mice, Inbred BALB C","RNA, Double-Stranded","Lymphocytes, Tumor-Infiltrating","CCAAT-Enhancer-Binding Proteins","Cell Line, Tumor","Mice","Tumor Microenvironment"],"keywords":["CEBPA","Cancer research","Immune system","Medicine","Immunotherapy","Biology","Immune checkpoint","Immunology","Transcription factor","Gene","PD-1","Abscopal"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T09:40:57.624662Z","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":[]}