{"doi":"10.3390/cancers13153798","title":"Human Wnt/β-Catenin Regulates Alloimmune Signaling during Allogeneic Transplantation","abstract":"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most widely applied forms of adoptive immunotherapy for the treatment of hematological malignancies. Detrimental graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia (GVL) effects occurring after allo-HSCT are largely mediated by alloantigen-reactive donor T cells in the graft. Separating GVHD from GVL effects is a formidable challenge, and a greater understanding of donor T cell biology is required to accomplish the uncoupling of GVHD from GVL. Here, we evaluated the role of β-catenin in this process. Using a unique mouse model of transgenic overexpression of human β-catenin (Cat-Tg) in an allo-HSCT model, we show here that T cells from Cat-Tg mice did not cause GVHD, and surprisingly, Cat-Tg T cells maintained the GVL effect. Donor T cells from Cat-Tg mice exhibited significantly lower inflammatory cytokine production and reduced donor T cell proliferation, while upregulating cytotoxic mediators that resulted in enhanced cytotoxicity. RNA sequencing revealed changes in the expression of 1169 genes for CD4, and 1006 genes for CD8+ T cells involved in essential aspects of immune response and GVHD pathophysiology. Altogether, our data suggest that β-catenin is a druggable target for developing therapeutic strategies to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.","journal":"Cancers","year":2021,"id":199287,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":490101,"name":"Rebecca Harris","orcid":"0000-0002-5854-4700","position":1,"is_corresponding":false},{"id":775304,"name":"Sara Mahmudlu","orcid":"0000-0002-0115-4576","position":2,"is_corresponding":false},{"id":264586,"name":"Anjali Verma","orcid":"0000-0003-4031-5966","position":3,"is_corresponding":false},{"id":717823,"name":"Adriana May","orcid":"0000-0003-3673-5626","position":4,"is_corresponding":false},{"id":775305,"name":"Rohan Dhawan","orcid":"0000-0002-1118-3514","position":5,"is_corresponding":false},{"id":471554,"name":"Adam T. Waickman","orcid":"0000-0002-4536-6714","position":6,"is_corresponding":false},{"id":264588,"name":"Jyoti Misra Sen","orcid":"0000-0002-6365-0866","position":7,"is_corresponding":false},{"id":302240,"name":"Avery August","orcid":"0000-0003-4968-3415","position":8,"is_corresponding":false},{"id":490105,"name":"Mobin Karimi","orcid":"0000-0002-3240-4814","position":9,"is_corresponding":false},{"id":491152,"name":"Mahinbanu Mammadli","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:50:36.595945Z","pmid":"34359702","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":[]}