ArticlebioRxiv : the preprint server for biology2025
Molecular Plasticity of T Cells Informs Their Possible Adaptation in 4T1 Tumors.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The triple-negative breast cancer (TNBC) microenvironment (TME) 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 molecular plasticity of T cells Objectives: To characterize transcriptional changes in T cells during TNBC progression and identify stage-specific shifts in T cell function, polarization, and antigen-presenting cell (APC)-T cell interactions. Results: Transcriptional analysis of T cells from BALB/c mice bearing 4T1 tumors at 1, 3, and 6 weeks revealed a decline in T cell-associated genes from 194 at 1 week to 156 at 6 weeks, with a significant late-stage loss of TCR diversity and contraction of natural killer T (NKT)- and γδ T cell-related transcripts. Cytokine and transcription factor dynamics reflected temporal T cell polarization: early (1 week) IL-12α/β-STAT4 signaling supports CD4 Conclusions: TNBC progression is characterized by progressive T cell functional decline, narrowing of TCR diversity, impaired APC-T cell interactions, and sustained macrophage-driven immunosuppression. These temporally coordinated immune shifts suggest tumor-driven adaptation toward immune evasion and identify potential windows for stage-specific immunotherapeutic intervention.
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