{"doi":"10.3390/cancers13061263","title":"Harnessing the IL-21-BATF Pathway in the CD8+ T Cell Anti-Tumor Response","abstract":"In cancer, CD8+ T cells enter a dysfunctional state which prevents them from effectively targeting and killing tumor cells. Tumor-infiltrating CD8+ T cells consist of a heterogeneous population of memory-like progenitor, effector, and terminally exhausted cells that exhibit differing functional and self-renewal capacities. Our recently published work has shown that interleukin (IL)-21-producing CD4+ T cells help to generate effector CD8+ T cells within the tumor, which results in enhanced tumor control. However, the molecular mechanisms by which CD4+ helper T cells regulate the differentiation of effector CD8+ T cells are not well understood. In this study, we found that Basic Leucine Zipper ATF-Like Transcription Factor (BATF), a transcription factor downstream of IL-21 signaling, is critical to maintain CD8+ T cell effector function within the tumor. Using mixed bone marrow chimeras, we demonstrated that CD8+ T cell-specific deletion of BATF resulted in impaired tumor control. In contrast, overexpressing BATF in CD8+ T cells enhanced effector function and resulted in improved tumor control, bypassing the need for CD4+ helper T cells. Transcriptomic analyses revealed that BATF-overexpressing CD8+ T cells had increased expression of costimulatory receptors, effector molecules, and transcriptional regulators, which may contribute to their enhanced activation and effector function. Taken together, our study unravels a previously unappreciated CD4+ T cell-derived IL-21–BATF axis that could provide therapeutic insights to enhance effector CD8+ T cell function to fight cancer.","journal":"Cancers","year":2021,"id":160285,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"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":642775,"name":"Gang Xin","orcid":"0000-0003-1963-505X","position":1,"is_corresponding":false},{"id":412055,"name":"Yao Chen","orcid":"0000-0001-5460-0149","position":2,"is_corresponding":false},{"id":672750,"name":"Shikan Zheng","orcid":"0000-0002-8968-9742","position":3,"is_corresponding":false},{"id":270587,"name":"Robert Burns","orcid":"0000-0001-5334-3486","position":4,"is_corresponding":false},{"id":302505,"name":"Jian Shen","orcid":"0000-0001-8398-2318","position":5,"is_corresponding":false},{"id":302501,"name":"Moujtaba Y. Kasmani","orcid":"0000-0002-5753-5335","position":6,"is_corresponding":false},{"id":672751,"name":"Matthew R. Kudek","orcid":"0000-0002-4140-6707","position":7,"is_corresponding":false},{"id":672752,"name":"Na Yang","orcid":"0000-0003-1383-1615","position":8,"is_corresponding":false},{"id":302507,"name":"Weiguo Cui","orcid":"0000-0003-1562-9218","position":9,"is_corresponding":false},{"id":349890,"name":"Paytsar Topchyan","orcid":"0000-0002-3902-7652","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:44:43.908634Z","pmid":"33809259","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":[]}