Immunoediting: evidence of the multifaceted role of the immune system in self-metastatic tumor growth.
Immunoediting: evidence of the multifaceted role of the immune system in self-metastatic tumor growth.
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免疫编辑：免疫系统在自我迁移肿瘤生长中的多方面作用的证据。
DOI：
10.1186/1742-4682-9-31
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发表时间：
2012-07-28
影响因子：
--
通讯作者：
Hahnfeldt P
中科院分区：
文献类型：
--
作者：
Enderling H;Hlatky L;Hahnfeldt P
免疫系统在肿瘤进展中的作用已经讨论了几十年。许多研究表明，低免疫应答可能对肿瘤生长有益（如果不是必要的话），只有强免疫应答才能对抗肿瘤生长，从而抑制进展。我们实现了先前描述的细胞自动机模型，该模型通过自我转移的过程捕获肿瘤的癌症干细胞和非干细胞群体之间的动态相互作用。通过在该模型上叠加免疫反应物从外周源到靶细胞扩散到肿瘤中，我们模拟了免疫系统诱导的细胞杀伤肿瘤进展的过程。低细胞毒性免疫反应持续杀死癌细胞，并且尽管以低速率，但由此导致空间受限的癌症干细胞的释放以驱动自身转移进展和持续的肿瘤生长。然而，随着免疫系统强度的增加，肿瘤生长达到峰值，然后最终福尔斯下降到没有免疫应答时观察到的固有肿瘤大小以下。随着这种免疫应答的增加，癌症干细胞的数量和比例单调增加，暗示了额外的意想不到的结果，即癌症干细胞选择对免疫应答的影响。癌症干细胞和免疫细胞毒性本身足以解释三步“免疫编辑”概念-通过抑制，选择和促进调节肿瘤生长。
The role of the immune system in tumor progression has been a subject for discussion for many decades. Numerous studies suggest that a low immune response might be beneficial, if not necessary, for tumor growth, and only a strong immune response can counter tumor growth and thus inhibit progression. We implement a cellular automaton model previously described that captures the dynamical interactions between the cancer stem and non-stem cell populations of a tumor through a process of self-metastasis. By overlaying on this model the diffusion of immune reactants into the tumor from a peripheral source to target cells, we simulate the process of immune-system-induced cell kill on tumor progression. A low cytotoxic immune reaction continuously kills cancer cells and, although at a low rate, thereby causes the liberation of space-constrained cancer stem cells to drive self-metastatic progression and continued tumor growth. With increasing immune system strength, however, tumor growth peaks, and then eventually falls below the intrinsic tumor sizes observed without an immune response. With this increasing immune response the number and proportion of cancer stem cells monotonically increases, implicating an additional unexpected consequence, that of cancer stem cell selection, to the immune response. Cancer stem cells and immune cytotoxicity alone are sufficient to explain the three-step “immunoediting” concept – the modulation of tumor growth through inhibition, selection and promotion.
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影响因子：
5.5
作者：
Enderling, Heiko;Hlatky, Lynn;Hahnfeldt, Philip
通讯作者：
Hahnfeldt, Philip
影响因子：
56.9
作者：
PREHN, RT
通讯作者：
PREHN, RT
影响因子：
11.2
作者：
Enderling, Heiko;Anderson, Alexander R. A.;Hahnfeldt, Philip
通讯作者：
Hahnfeldt, Philip
影响因子：
3.7
作者：
Levina V;Marrangoni AM;DeMarco R;Gorelik E;Lokshin AE
通讯作者：
Lokshin AE
影响因子：
--
作者：
Kuznetsov, VA;Knott, GD
通讯作者：
Knott, GD