通过分析肿瘤浸润的CD4+和CD8+ CDR3序列，揭示了可能与抗肿瘤免疫应答相关的共同特征。
Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response.
发表日期：2023
作者：
Andrea Aran, Gonzalo Lázaro, Vicente Marco, Elisa Molina, Ferran Abancó, Vicente Peg, María Gión, Laia Garrigós, José Pérez-García, Javier Cortés, Mercè Martí
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
肿瘤浸润淋巴细胞（TILs）在乳腺癌（BC）中具有预测和预后价值，并对抗肿瘤生长起到保护作用，表明可采用TILs或基于T细胞受体（TCR）的治疗方法进行治疗。TCR可用于鉴定自然对肿瘤具有反应性的T细胞，但目前对CD4+和CD8+ TILs的TCR重组序列差异知之甚少。本研究使用多通路测序技术对来源于11例BC活检的TILs进行了测序，此外，还使用相同方法对正常供体的PBMCs进行了扩增和排序。观察到T细胞亚群之间的物理化学TCR差异，其中CD4+ TILs呈现出较大的N(D)Nnt TRB序列，并具有更高的正电荷残基使用率，尽管仅有后者也观察到在来自健康人外周T细胞中同样存在。此外，在CD4+ TILs中，观察到更为有限的TCR重组序列和较高数量的包含特定氨基酸模体的类似序列。CD4+和CD8+ TCR之间的某些差异是T细胞亚群固有的，可以在来自健康人外周T细胞中观察到，而其他差异仅在TIL样本中发现，因此可能是由于肿瘤所致。值得注意的是，CD4+ TCR之间更高的相似性表明这个亚群在TCR的多样性上更为杂交。版权所有©2023 Aran, Lázaro, Marco, Molina, Abancó, Peg, Gión, Garrigós, Pérez-García, Cortés and Martí.
Tumor-infiltrating lymphocytes (TILs) have predictive and prognostic value in breast cancer (BC) and exert a protective function against tumor growth, indicating that it is susceptible to treatment using adoptive cell transfer of TILs or T cell receptor (TCR)-based therapies. TCR can be used to identify naturally tumor-reactive T cells, but little is known about the differences in the TCR repertoires of CD4+ and CD8+ TILs.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.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.Copyright © 2023 Aran, Lázaro, Marco, Molina, Abancó, Peg, Gión, Garrigós, Pérez-García, Cortés and Martí.