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分析肿瘤浸润性 CD4+和 CD8+ CDR3 序列揭示与抗肿瘤免疫应答推定相关的共有特征

英文原题:Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response.

查看英文原题

Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response.

PubMed 2023/08/04(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

CD4+和 CD8+ TCR 之间的一些差异是 T 细胞亚群固有的,这也可以从健康个体的外周 T 细胞中观察到,而其他差异仅在 TILs 样本中发现,因此可能是肿瘤驱动的。值得注意的是,CD4+ TCR 之间更高的相似性表明该亚群中 TCR 的混杂性更高。

研究思路结论见上方概要

TIL(肿瘤浸润淋巴细胞)(TILs)在乳腺癌(BC)中具有预测和预后价值,并对肿瘤生长发挥保护作用,表明其易受TILs过继细胞转移或基于T细胞受体(TCR)的治疗。TCR可用于识别天然肿瘤反应性T细胞,但关于CD4+和CD8+ TILs的TCR库差异知之甚少。

对来自11例BC活检初始培养的TIL,以及扩增并分选的CD4+和CD8+ TIL进行了TCR高通量测序,同时对健康供体外周血单个核细胞(PBMC)采用相同方法扩增并分选后也进行了测序。

观察到T细胞亚群之间存在TCR的理化差异,因为CD4+ TIL呈现更长的N(D)Nnt TRB序列,并且带正电荷残基的使用率更高,尽管后者也仅在健康个体的外周T细胞中观察到。此外,在CD4+ TIL中,观察到TCR库更为受限,含有特定氨基酸基序的相似序列丰度更高。

展开英文摘要原文

TCR high-throughput sequencing was performed using TILs derived from the initial cultures of 11 BC biopsies and expanded and sorted CD4+ and CD8+ TILs as well as using PBMCs from healthy donors expanded and sorted using the same methodology.

Physicochemical TCR differences between T cell subsets were observed, as CD4+ TILs presented larger N(D)Nnt TRB sequences and with a higher usage of positively charged residues, although only the latest was also observed in peripheral T cells from healthy individuals. Moreover, in CD4+ TILs, a more restricted TCR repertoire with a higher abundance of similar sequences containing certain amino acid motifs was observed. DISCUSSION: Some differences between CD4+ and CD8+ TCRs were intrinsic to T cell subsets as can also be observed in peripheral T cells from healthy individuals, while other were only found in TILs samples and therefore may be tumor-driven. Notably, the higher similarity among CD4+ TCRs suggests a higher TCR promiscuity in this subset.

论文信息

作者
Aran A、Lázaro G、Marco V、Molina E、Abancó F、Peg V、Gión M、Garrigós L
单位
Immunology Unit, Department of Cell Biology, Physiology, and Immunology, Institut de Biotecnologia i Biomedicina (IBB), Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain.Spain
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2023
原文标识
PubMed 37600765 · DOI 10.3389/fimmu.2023.1227766