Accumulation of an endogenous tryptophan-derived metabolite in colorectal and breast cancers.
Accumulation of an endogenous tryptophan-derived metabolite in colorectal and breast cancers.
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DOI：
10.1371/journal.pone.0122046
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Guillemin GJ
中科院分区：
文献类型：
--
作者：
Puccetti P;Fallarino F;Italiano A;Soubeyran I;MacGrogan G;Debled M;Velasco V;Bodet D;Eimer S;Veldhoen M;Prendergast GC;Platten M;Bessede A;Guillemin GJ
肿瘤免疫逃逸机制被认为是肿瘤治疗的合适靶点。其中，色氨酸催化剂在创造免疫抑制环境中起着核心作用，导致对潜在免疫原性肿瘤抗原的耐受性。色氨酸催化剂由吲哚胺2，3-双加氧酶（IDO-1/-2）或色氨酸2，3-双加氧酶2（TDO 2）启动，导致生物静态色氨酸饥饿和l-犬尿氨酸产生，其参与塑造宿主免疫系统与肿瘤细胞的动态关系。目前的免疫治疗策略包括阻断IDO-1/-2或TDO 2，以恢复有效的抗肿瘤反应。目前基于肿瘤组织中IDO-1/-2或TD 0 2的表达分析和/或通过血清中犬尿氨酸/色氨酸比率评估的酶活性来鉴定可能受益于该方法的患者。我们开发了靶向l-犬尿氨酸的单克隆抗体作为IDO-1/-2或TDO 2活性的原位生物标志物。使用组织微阵列技术和免疫染色，基于l-犬尿氨酸的产生对结肠直肠癌和乳腺癌患者进行表型分型。在结直肠癌中，l-犬尿氨酸与IDO-1表达没有明确相关性，表明单纯色氨酸分解代谢酶的表达对于最佳免疫疗法来说不足以提供信息。
Tumor immune escape mechanisms are being regarded as suitable targets for tumor therapy. Among these, tryptophan catabolism plays a central role in creating an immunosuppressive environment, leading to tolerance to potentially immunogenic tumor antigens. Tryptophan catabolism is initiated by either indoleamine 2,3-dioxygenase (IDO-1/-2) or tryptophan 2,3-dioxygenase 2 (TDO2), resulting in biostatic tryptophan starvation and l-kynurenine production, which participates in shaping the dynamic relationship of the host’s immune system with tumor cells. Current immunotherapy strategies include blockade of IDO-1/-2 or TDO2, to restore efficient antitumor responses. Patients who might benefit from this approach are currently identified based on expression analyses of IDO-1/-2 or TDO2 in tumor tissue and/or enzymatic activity assessed by kynurenine/tryptophan ratios in the serum. We developed a monoclonal antibody targeting l-kynurenine as an in situ biomarker of IDO-1/-2 or TDO2 activity. Using Tissue Micro Array technology and immunostaining, colorectal and breast cancer patients were phenotyped based on l-kynurenine production. In colorectal cancer l-kynurenine was not unequivocally associated with IDO-1 expression, suggesting that the mere expression of tryptophan catabolic enzymes is not sufficiently informative for optimal immunotherapy.
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影响因子：
16.8
作者：
Munn DH;Mellor AL
通讯作者：
Mellor AL
影响因子：
5.3
作者：
Suzuki, Yuzo;Suda, Takafumi;Chida, Kingo
通讯作者：
Chida, Kingo
影响因子：
11.5
作者：
Brandacher, G;Perathoner, A;Amberger, A
通讯作者：
Amberger, A
DOI：
10.1073/pnas.1113873109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Pilotte, Luc;Larrieu, Pierre;Van den Eynde, Benoit J.
通讯作者：
Van den Eynde, Benoit J.
影响因子：
2.8
作者：
Sperner-Unterweger, Barbara;Neurauter, Gabriele;Fuchs, Dietmar
通讯作者：
Fuchs, Dietmar