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T细胞的分子可塑性告知了它们在4T1瘤中的可能适应性

Md Iftehimul¹, Robert H Newman², Scott H Harrison²

¹Institute of Biotechnology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh.

bioRxiv : the preprint server for biology

|November 24, 2025

概括

三重阴性乳腺癌 (TNBC) 的进展涉及T细胞功能下降和免疫细胞相互作用受损. 了解瘤微环境 (TME) 中的这些变化为向免疫疗法提供了机会.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
分子生物学分子生物学

背景情况:

在三阴性乳腺癌 (TNBC) 中的瘤微环境 (TME) 在进展过程中从免疫活性转变为免疫抑制.
虽然已知瘤细胞的可塑性,但在TNBC进展过程中体内T细胞的分子可塑性尚不清楚.

研究的目的:

在TNBC进展过程中调查T细胞的转录性变化.
为了确定T细胞功能,两极分化和与抗原呈现细胞 (APC) 的相互作用的特定阶段的变化.

主要方法:

植入后1,3周和6周,从BALB/c小鼠获得4T1瘤的T细胞的转录分析.
分析与T细胞功能,细胞因子信号传递和APC-T细胞相互作用相关的基因表达.

主要成果:

从第1周到第6周观察到T细胞相关基因和TCR多样性的减少.
细胞因子信号传递的时间变化表明两极化变化:早期的Th1/Tc1,短暂的Tfc和晚期的Tc17/Tc22反应.
在晚期TNBC中明显出现了受损的APC-T细胞交叉和持续的巨驱动免疫抑制.

结论:

TNBC进展的标志是T细胞功能下降,TCR多样性减少和APC相互作用受损.
这些免疫变化表明瘤适应免疫逃避.
这些发现突出了TNBC中特定阶段免疫疗法的潜在治疗窗口.

关键词:

4T1 一个人的生活在T细胞,T细胞.瘤的适应瘤的适应适应适应适应适应现型性可塑性现型性可塑性三重阴性乳腺癌 (TNBC) 是一种

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