{"doi":"10.1016/j.csbj.2025.12.022","title":"Temporal molecular remodeling of T cells informs their possible adaptation in 4T1 tumors","abstract":"Abstract Background The triple-negative breast cancer (TNBC) microenvironment undergoes progressive reprogramming, transitioning from an early immune-active state to a late immune-suppressed state. While tumor cell plasticity has been extensively studied, the temporal molecular remodeling of T cells in vivo remains poorly defined. Results Transcriptional analysis of T cells within 4T1 TNBC tumors, harvested at one-, three-, and six-weeks post-tumor implantation in the mammary fat pads of BALB/c mice, revealed a decline in transcriptomic signatures associated with T cells from 194 at one week to 156 at six weeks, with a significant late-stage loss or reduction of transcripts related to T cell receptors (TCR), natural killer T, and gamma delta T cells. Furthermore, changes in various temporal signature genes specific to T cell cytokines and transcription factors reflected temporal T cell polarization to CD4 + type 1 T helper and type 1 CD8 + cytotoxic T cell responses at one week, CD8 + cytotoxic follicular T cell skewing at three weeks, and interleukin 17/22 producing CD8 + T cell transition at six weeks. The antigen-presenting cell (APC) transcripts deteriorated at six weeks, characterized by reduced expression of co-stimulatory and APC genes. Despite an early dominance of M1-like macrophage genes (e.g., IL-12α/β ), persistent expression of arginase 1 ( ARG1 ) and other M2-associated genes indicated a stable tolerogenic niche. Conclusions The temporally coordinated immune shifts, such as progressive decline in transcripts associated with T cell functions, TCRs, APCs, and sustained macrophage-driven immunosuppression, suggest tumor-driven adaptation toward immune evasion and identify potential windows for stage-specific immunotherapeutic intervention.","journal":"Computational and Structural Biotechnology Journal","year":2025,"id":537736,"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":0.9101,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":310397,"name":"Robert H. Newman","orcid":"0000-0002-3865-0266","position":1,"is_corresponding":false},{"id":1232266,"name":"Scott H. Harrison","orcid":"0000-0002-9577-445X","position":2,"is_corresponding":false},{"id":247725,"name":"Roshonda B. Jones","orcid":"0000-0003-1637-3517","position":3,"is_corresponding":false},{"id":1423994,"name":"Perpetua M. Muganda","orcid":"0000-0001-5928-6822","position":4,"is_corresponding":false},{"id":668093,"name":"Bryan L. Holloman","orcid":"0000-0002-9891-9001","position":5,"is_corresponding":false},{"id":1149082,"name":"M. Hossain","orcid":"0009-0003-2489-2672","position":6,"is_corresponding":false},{"id":1377139,"name":"Checo J. Rorie","orcid":"0000-0002-7130-6790","position":7,"is_corresponding":false},{"id":942064,"name":"Misty D. Thomas","orcid":"0000-0001-9039-4098","position":8,"is_corresponding":false},{"id":713263,"name":"Joseph L. Graves","orcid":"0000-0001-8446-1709","position":9,"is_corresponding":false},{"id":364576,"name":"Howard L. Kaufman","orcid":"0000-0003-1131-004X","position":10,"is_corresponding":false},{"id":348242,"name":"Dipongkor Saha","orcid":"0000-0002-9923-5533","position":11,"is_corresponding":false},{"id":1424409,"name":"Md. Iftehimul","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:52:16.891390Z","pmid":"41550137","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":[]}