{"doi":"10.1007/s00262-025-04247-1","title":"Pomalidomide enhances CAR-T cell therapeutic efficacy and remodels immune microenvironment in lymphoid malignancies","abstract":null,"journal":"Cancer Immunology, Immunotherapy","year":2025,"id":645586,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"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":329211,"name":"Yan Yu","orcid":"0000-0002-5210-3971","position":1,"is_corresponding":false},{"id":1681094,"name":"Linzhi Xie","orcid":null,"position":2,"is_corresponding":false},{"id":228965,"name":"Liwen Wang","orcid":"0000-0002-0297-9553","position":3,"is_corresponding":false},{"id":948913,"name":"Yuhan Yan","orcid":null,"position":4,"is_corresponding":false},{"id":215552,"name":"Qian Cheng","orcid":null,"position":5,"is_corresponding":false},{"id":756065,"name":"Jing Liu","orcid":"0000-0002-3588-2969","position":6,"is_corresponding":false},{"id":1681095,"name":"Chang Zhang","orcid":null,"position":7,"is_corresponding":false},{"id":898691,"name":"Xin Li","orcid":"0000-0001-9024-7522","position":8,"is_corresponding":false},{"id":278051,"name":"Yi Zhou","orcid":"0000-0001-9024-7514","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Pomalidomide enhances CAR-T cell therapeutic efficacy and remodels immune microenvironment in lymphoid malignancies","abstract":"BACKGROUND: Chimeric antigen receptor T cell (CAR-T) therapy achieves high remission rates in lymphoid malignancies, but its long-term efficacy is limited by poor persistence and T cell exhaustion. Pomalidomide, an immunomodulatory drug (IMiD), demonstrates clinical synergy with CAR-T therapy, yet the underlying mechanisms driving this potentiation remain poorly defined. This study aimed to elucidate how pomalidomide enhances CAR-T cell function and remodels the immune microenvironment to overcome therapeutic limitations. METHODS: In vitro assays (CCK-8, LDH, qPCR, ELISA, flow cytometry) and bulk RNA-seq assessed pomalidomide's effects on human CAR-T cells. In vivo efficacy was evaluated in myeloma xenograft models. Single-cell RNA sequencing (scRNA-seq) of PBMCs from a lymphoma patient post-CAR-T/pomalidomide assessed immune microenvironment remodeling. RESULTS: Pomalidomide significantly enhanced CAR-T cell proliferation and cytotoxicity in an activation-dependent manner. It upregulated effector molecules (IL-2, IFN-γ) and chemokines (CXCL9-CXCL11), promoted central memory T cells (Tcm), and induced metabolic reprogramming while reducing exhaustion markers. In xenografts, combination therapy induced tumor regression and extended survival vs. CAR-T alone. scRNA-seq revealed pomalidomide-driven remodeling, characterized by increased T/NK cell proportions/activity and reduced myeloid-derived suppressor cell (MDSC) signatures. CONCLUSIONS: Pomalidomide synergizes with CAR-T by directly enhancing CAR-T function (memory, cytokine/chemokine production, metabolic fitness, and reduced exhaustion) and remodeling the suppressive immune microenvironment (increased cytotoxic effectors, diminished MDSC activity). These findings provide a crucial mechanistic rationale for optimizing pomalidomide-CAR-T combinations in refractory lymphoid malignancies.","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41410870","pmcid":"PMC12715080","openalex_id":"https://openalex.org/W4417459029","authors":[],"funders":[{"funder_name":"Fundamental Research Funds for Central Universities of the Central South University","grant_id":"2025ZZTS0194","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82170204","title":null},{"funder_name":"Beijing Medical and Health Foundation","grant_id":"JSZ021","title":null}],"total_grants":3,"fwci":0.4926,"citation_percentile":0.72142086,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s00262-025-04247-1.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s00262-025-04247-1.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s00262-025-04247-1","host_type":"publisher"},{"url":"https://doi.org/10.1007/s00262-025-04247-1","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41410870","host_type":"repository"},{"url":"https://doaj.org/article/c6db848d5ac04bcf995352a467b0cf7e","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12715080/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12715080","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12715080?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["CAR-T cell therapy research","T-cell and B-cell Immunology","Protein Degradation and Inhibitors","Thalidomide","Humans","Animals","Tumor Microenvironment","Mice","Immunotherapy, Adoptive","Xenograft Model Antitumor Assays","Receptors, Chimeric Antigen","Multiple Myeloma","Cell Line, Tumor","Lymphoma"],"mesh_terms":["Receptors, Chimeric Antigen","Animals","Humans","Lymphoma","Multiple Myeloma","Thalidomide","Immunotherapy, Adoptive","Xenograft Model Antitumor Assays","Cell Line, Tumor","Mice","Tumor Microenvironment"],"keywords":["Pomalidomide","Tumor microenvironment","Immune system","Immunotherapy","Cytotoxic T cell","Function (biology)","Refractory (planetary science)","T cell","Memory T Cell","Immune Microenvironment","Lymphoid Malignancies","Car-t Therapy"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T09:23:42.652275Z","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":[]}