Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells,European Journal of Immunology

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Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells
European Journal of Immunology ( IF 4.5 ) Pub Date : 2021-06-03 , DOI: 10.1002/eji.202049103
Francesco Manfredi _{1,

2} , Danilo Abbati ₁ , Beatrice Claudia Cianciotti ₁ , Lorena Stasi ₂ , Alessia Potenza _{1,

3} , Eliana Ruggiero ₁ , Zulma Magnani ₁ , Erica Carnevale ₁ , Matteo Doglio _{1,

2} , Maddalena Noviello ₁ , Elena Tassi ₁ , Chiara Balestrieri ₁ , Silvia Buonanno ₁ , Francesca Clemente ₄ , Claudia De Lalla ₅ , Maria Pia Protti ₄ , Anna Mondino ₆ , Giulia Casorati ₅ , Paolo Dellabona ₅ , Chiara Bonini _{1,

2}

Affiliation

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.

中文翻译：

cytoChain 流式细胞术数据挖掘确定 TCR 工程化 T 细胞耗竭和干性的决定因素

注入细胞的表型是过继 T 细胞疗法 (ACT) 疗效的主要决定因素。然而，破译多参数细胞计数数据的困难限制了细胞产品的精细表征。为了能够分析动态和复杂的流式细胞术样本，我们开发了 cytoChain，这是一种新型的数据集挖掘工具和一种新的分析工作流程。CytoChain 面临的挑战是比较最先进和创新的培养条件，以生成适用于 ACT 的干细胞样记忆细胞 (T _SCM )。值得注意的是，IL-7/15 和超氧化物清除的组合维持了以前未鉴定的未耗尽 Fit-T _{SCM 的出现}签名，被手动门控忽略并赋予了卓越的扩展潜力。CytoChain 在独立数据集和 T 细胞受体工程淋巴细胞中熟练地追溯了这一群体。然后在来自 COVID-19 患者循环 T 细胞的已发布数据集上进一步验证了 CytoChain 的灵活性和功能。总的来说，我们的结果支持使用 cytoChain 来识别新的、功能关键的 ACT 免疫表型和患者免疫监测。

更新日期：2021-08-05

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