A systems immunology approach to the host-tumor interaction: large-scale patterns of natural autoantibodies distinguish healthy and tumor-bearing mice.
A systems immunology approach to the host-tumor interaction: large-scale patterns of natural autoantibodies distinguish healthy and tumor-bearing mice.
复制标题
DOI：
10.1371/journal.pone.0006053
复制
发表时间：
2009-06-25
期刊：
影响因子：
3.7
通讯作者：
Cohen IR
中科院分区：
文献类型：
--
作者：
Merbl Y;Itzchak R;Vider-Shalit T;Louzoun Y;Quintana FJ;Vadai E;Eisenbach L;Cohen IR
传统上，免疫学认为有意义的抗体反应是由大量的高亲和力抗体与特定的刺激抗原反应所标记的；检测到少量的低亲和力抗体结合似乎不相关的抗原被认为是低于免疫学意义的阈值。然而，免疫学的系统生物学方法表明，抗体库中的大规模模式也可能反映免疫系统的功能状态。为了研究这种抗体的全局模式，我们使用了抗原微阵列设备结合信息学分析。在这里，我们询问抗体库模式是否可以反映植入肿瘤的状态。我们研究了近交系C57BL/6小鼠在转移性和非转移性克隆的同基因3LL肿瘤细胞植入前后的血清抗体。我们使用支持向量机和遗传算法技术分析了IgG和IgM自身抗体与300多种自身抗原的结合模式。我们现在报告了抗体模式，而不是单一抗体，提供了信息：1)小鼠，甚至在肿瘤植入之前，表现出个体和共同的低滴度天然自身抗体模式；2)这些自身抗体的模式对肿瘤细胞的生长有反应，并能区分转移性和非转移性肿瘤克隆；3)根治性肿瘤切除引起这些低效价自身抗体模式的动态变化。信息模式包括自身抗体结合的自身分子不知道是肿瘤相关抗原（包括胰岛素，DNA，肌球蛋白，纤维蛋白原），以及已知的肿瘤相关抗原（包括p53，细胞角蛋白，碳酸酐酶，酪氨酸酶）。因此，不是肿瘤特异性免疫直接产物的低滴度自身抗体仍然可以产生机体-肿瘤相互作用的免疫生物标志物。系统范围的自身抗体谱分析可以提供信息。
Traditionally, immunology has considered a meaningful antibody response to be marked by large amounts of high-affinity antibodies reactive with the specific inciting antigen; the detection of small amounts of low-affinity antibodies binding to seemingly unrelated antigens has been considered to be beneath the threshold of immunological meaning. A systems-biology approach to immunology, however, suggests that large-scale patterns in the antibody repertoire might also reflect the functional state of the immune system. To investigate such global patterns of antibodies, we have used an antigen-microarray device combined with informatic analysis. Here we asked whether antibody-repertoire patterns might reflect the state of an implanted tumor. We studied the serum antibodies of inbred C57BL/6 mice before and after implantation of syngeneic 3LL tumor cells of either metastatic or non-metastatic clones. We analyzed patterns of IgG and IgM autoantibodies binding to over 300 self-antigens arrayed on slides using support vector machines and genetic algorithm techniques. We now report that antibody patterns, but not single antibodies, were informative: 1) mice, even before tumor implantation, manifest both individual and common patterns of low-titer natural autoantibodies; 2) the patterns of these autoantibodies respond to the growth of the tumor cells, and can distinguish between metastatic and non-metastatic tumor clones; and 3) curative tumor resection induces dynamic changes in these low-titer autoantibody patterns. The informative patterns included autoantibodies binding to self-molecules not known to be tumor-associated antigens (including insulin, DNA, myosin, fibrinogen) as well as to known tumor-associated antigens (including p53, cytokeratin, carbonic anhydrases, tyrosinase). Thus, low-titer autoantibodies that are not the direct products of tumor-specific immunization can still generate an immune biomarker of the body-tumor interaction. System-wide profiling of autoantibody repertoires can be informative.
登录
查看更多内容
DOI：
10.1073/pnas.85.12.4463
发表时间：
1988-06-01
影响因子：
11.1
作者：
PLAKSIN, D;GELBER, C;EISENBACH, L
通讯作者：
EISENBACH, L
影响因子：
46.9
作者：
Robinson, WH;Fontoura, P;Steinman, L
通讯作者：
Steinman, L
影响因子：
82.9
作者：
Robinson, WH;DiGennaro, C;Utz, PJ
通讯作者：
Utz, PJ
影响因子：
--
作者：
Hueber, W;Kidd, BA;Robinson, WH
通讯作者：
Robinson, WH
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y