Molecular Plasticity of T Cells Informs Their Possible Adaptation in 4T1 Tumors

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• The tumor microenvironment (TME) in triple-negative breast cancer (TNBC) shifts from immune-active to immune-suppressed during progression.
• While tumor cell plasticity is known, the molecular plasticity of T cells in vivo during TNBC progression is not well understood.

Purpose of the Study:

• To investigate transcriptional alterations in T cells throughout TNBC progression.
• To identify stage-specific changes in T cell function, polarization, and interactions with antigen-presenting cells (APCs).

Main Methods:

• Transcriptional analysis of T cells from BALB/c mice with 4T1 tumors at 1, 3, and 6 weeks post-implantation.
• Analysis of gene expression related to T cell function, cytokine signaling, and APC-T cell interactions.

Main Results:

• A decrease in T cell-associated genes and TCR diversity was observed from week 1 to week 6.
• Temporal shifts in cytokine signaling indicated polarization changes: early Th1/Tc1, transient Tfc, and late Tc17/Tc22 responses.
• Impaired APC-T cell crosstalk and sustained macrophage-driven immunosuppression were evident in late-stage TNBC.

Conclusions:

• TNBC progression is marked by declining T cell function, reduced TCR diversity, and compromised APC interactions.
• These immune changes suggest tumor adaptation for immune evasion.
• The findings highlight potential therapeutic windows for stage-specific immunotherapies in TNBC.