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Abstract：
BACKGROUND: Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown promising results in cancer treatment, including breast cancer. However, clonal dynamics and clinical significance of TIL expansion ex vivo remain poorly understood.
METHODS: We investigated T cell receptor (TCR) repertoire changes in expanded TILs from 19 patients with breast cancer. We compared TCR repertoire of TILs at different stages of expansion, including initial (2W TILs) and rapid expansion (REP TILs), and their overlap with formalin fixed paraffin embedded (FFPE) and peripheral blood. Additionally, we examined differences in TCR repertoire between CD4+ and CD8+ REP TILs.
RESULTS: In descending order of proportion, average of 60% of the top 10% clonotypes of FFPE was retained in 2W TIL (60% in TRB, 64.7% in TRA). Among the overlapped clonotypes between 2W TILs and REP TILs, 69.9% was placed in top 30% of 2W TIL. The proportion of clonotypes in 2W TIL and REP TIL showed a significant positive correlation. CD4+ and CD8+ T cells show similar results in diversity and CDR3 length.
CONCLUSIONS: Our study traces the changes in TILs repertoire from FFPE to 2W TIL and REP TIL and confirmed that clonotypes with high frequencies in TILs have a high likelihood of maintaining their priority throughout culture process.
METHODS: We investigated T cell receptor (TCR) repertoire changes in expanded TILs from 19 patients with breast cancer. We compared TCR repertoire of TILs at different stages of expansion, including initial (2W TILs) and rapid expansion (REP TILs), and their overlap with formalin fixed paraffin embedded (FFPE) and peripheral blood. Additionally, we examined differences in TCR repertoire between CD4+ and CD8+ REP TILs.
RESULTS: In descending order of proportion, average of 60% of the top 10% clonotypes of FFPE was retained in 2W TIL (60% in TRB, 64.7% in TRA). Among the overlapped clonotypes between 2W TILs and REP TILs, 69.9% was placed in top 30% of 2W TIL. The proportion of clonotypes in 2W TIL and REP TIL showed a significant positive correlation. CD4+ and CD8+ T cells show similar results in diversity and CDR3 length.
CONCLUSIONS: Our study traces the changes in TILs repertoire from FFPE to 2W TIL and REP TIL and confirmed that clonotypes with high frequencies in TILs have a high likelihood of maintaining their priority throughout culture process.
摘要：
背景：使用肿瘤浸润淋巴细胞（TIL）的过继细胞疗法在癌症治疗中显示出可喜的结果，包括乳腺癌.然而,体外TIL扩增的克隆动力学和临床意义仍然知之甚少。
方法：我们研究了19例乳腺癌患者的T细胞受体（TCR）库的变化。我们比较了TIL在不同扩展阶段的TCR库，包括初始(2WTIL)和快速扩展(REPTIL)，与福尔马林固定石蜡包埋（FFPE）和外周血重叠。此外,我们检查了CD4+和CD8+REPTILs之间TCR库的差异。
结果：按比例降序排列，平均60%前10%的FFPE克隆型保留在2WTIL中(60%在TRB中，TRA中的64.7%）。在2WTIL和REPTIL之间的重叠克隆型中，69.9%位于2WTIL的前30%。2WTIL与REPTIL的克隆型比例呈显著正相干。CD4+和CD8+T细胞在多样性和CDR3长度方面显示相似的结果。
结论：我们的研究追踪了从FFPE到2WTIL和REPTIL的TIL库的变化，并证实TIL中具有高频率的克隆型很有可能在整个培养过程中保持其优先级。
方法：我们研究了19例乳腺癌患者的T细胞受体（TCR）库的变化。我们比较了TIL在不同扩展阶段的TCR库，包括初始(2WTIL)和快速扩展(REPTIL)，与福尔马林固定石蜡包埋（FFPE）和外周血重叠。此外,我们检查了CD4+和CD8+REPTILs之间TCR库的差异。
结果：按比例降序排列，平均60%前10%的FFPE克隆型保留在2WTIL中(60%在TRB中，TRA中的64.7%）。在2WTIL和REPTIL之间的重叠克隆型中，69.9%位于2WTIL的前30%。2WTIL与REPTIL的克隆型比例呈显著正相干。CD4+和CD8+T细胞在多样性和CDR3长度方面显示相似的结果。
结论：我们的研究追踪了从FFPE到2WTIL和REPTIL的TIL库的变化，并证实TIL中具有高频率的克隆型很有可能在整个培养过程中保持其优先级。
