A mathematical model for the quantification of a patient's sensitivity to checkpoint inhibitors and long-term tumour burden.
A mathematical model for the quantification of a patient's sensitivity to checkpoint inhibitors and long-term tumour burden.
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DOI：
10.1038/s41551-020-00662-0
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发表时间：
2021-04
影响因子：
28.1
通讯作者：
Cristini V
中科院分区：
文献类型：
--
作者：
Butner JD;Wang Z;Elganainy D;Al Feghali KA;Plodinec M;Calin GA;Dogra P;Nizzero S;Ruiz-Ramírez J;Martin GV;Tawbi HA;Chung C;Koay EJ;Welsh JW;Hong DS;Cristini V
很大一部分癌症患者对免疫检查点阻断和其他免疫疗法的治疗没有反应。在这里，我们报告了一个关于肿瘤对免疫检查点抑制剂反应的时间过程的数学模型。该模型考虑了固有的肿瘤生长率、免疫激活率和肿瘤-免疫-细胞相互作用的速率，以及免疫介导的肿瘤杀伤效果。对于124名患者，四种癌症类型和两种免疫治疗药物，该模型可靠地描述了所有不同癌症和药物组合检查的免疫反应和最终肿瘤负担。在四项检查点抑制剂临床试验(总共177名患者)的验证队列中，该模型根据减少或增加的长期肿瘤负担对患者进行了准确的分层。我们还提供了针对特定药物-癌症组合的治疗敏感性的模型派生的定量测量。该模型可用于预测对治疗的反应，并对个别患者的特定药物-癌症敏感性进行量化。
A large proportion of patients with cancer are unresponsive to treatment with immune checkpoint blockade and other immunotherapies. Here, we report a mathematical model of the time-course of tumour responses to immune-checkpoint inhibitors. The model takes into account intrinsic tumour-growth rates, the rates of immune activation and of tumour–immune-cell interactions, and the efficacy of immune-mediated tumour killing. For 124 patients, four cancer types and two immunotherapy agents, the model reliably described the immune responses and final tumour burden across all different cancers and drug combinations examined. In validation cohorts from four clinical trials of checkpoint inhibitors (with a total of 177 patients), the model accurately stratified the patients according to reduced or increased long-term tumour burden. We also provide model-derived quantitative measures of treatment sensitivity for specific drug–cancer combinations. The model can be used to predict responses to therapy and to quantify specific drug–cancer sensitivities in individual patients.
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影响因子：
16.6
作者：
Dogra P;Adolphi NL;Wang Z;Lin YS;Butler KS;Durfee PN;Croissant JG;Noureddine A;Coker EN;Bearer EL;Cristini V;Brinker CJ
通讯作者：
Brinker CJ
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
4.6
作者：
Brocato TA;Coker EN;Durfee PN;Lin YS;Townson J;Wyckoff EF;Cristini V;Brinker CJ;Wang Z
通讯作者：
Wang Z
影响因子：
13.6
作者：
Butner, Joseph D.;Elganainy, Dalia;Cristini, Vittorio
通讯作者：
Cristini, Vittorio
DOI：
10.1146/annurev-bioeng-071910-124729
发表时间：
2011-08-15
影响因子：
9.7
作者：
Deisboeck TS;Wang Z;Macklin P;Cristini V
通讯作者：
Cristini V