Philip Hagit, Snir Tom, Gordin Miri, Shugay Mikhail, Zilberberg Alona, Efroni Sol
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
iScience. 2021 Jan 27;24(2):102100. doi: 10.1016/j.isci.2021.102100. eCollection 2021 Feb 19.
Biology of the response to anti-CTLA-4 involves the dynamics of specific T cell clones. Reasons for clinical success and failure of this treatment are still largely unknown. Here, we quantified the dynamics of the T cell receptor (TCR) repertoire, throughout 4 weeks involving treatment with anti-CTLA-4, in a syngeneic mouse model for colorectal cancer. These dynamics show an initial increase in clonality in tandem with a decrease in diversity, effects which gradually subside. Furthermore, response to treatment is tightly connected to the shared and public parts of the T cell repertoire. We were able to recognize time-dependent behaviors of specific TCR sequences and cell types and to show the response is dominated by specific motifs. We see that a single, specific time point might be useful to inform a physician of the true response to treatmentThe research further highlights the importance of temporal analyses of the immune response.
抗CTLA-4治疗反应的生物学机制涉及特定T细胞克隆的动态变化。这种治疗临床成败的原因在很大程度上仍不明确。在此，我们在同基因小鼠结直肠癌模型中，对抗CTLA-4治疗4周期间的T细胞受体（TCR）库动态变化进行了量化。这些动态变化显示克隆性最初增加，同时多样性降低，这些效应逐渐消退。此外，治疗反应与T细胞库的共享和公共部分紧密相关。我们能够识别特定TCR序列和细胞类型的时间依赖性行为，并表明反应由特定基序主导。我们发现，单个特定时间点可能有助于告知医生治疗的真实反应。该研究进一步凸显了免疫反应时间分析的重要性。
