Variable indoleamine 2,3-dioxygenase expression in acral/mucosal melanoma and its possible link to immunotherapy
Variable indoleamine 2,3-dioxygenase expression in acral/mucosal melanoma and its possible link to immunotherapy
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DOI：
10.1111/cas.14195
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发表时间：
2019-09-30
期刊：
影响因子：
5.7
通讯作者：
Kabashima, Kenji
中科院分区：
文献类型：
--
作者：
Iga, Natsuko;Otsuka, Atsushi;Kabashima, Kenji
免疫检查点抑制剂改善了晚期黑色素瘤的预后。尽管抗程序性死亡配体-1 （PD-L1）是黑色素瘤中抗程序性死亡-1 PD-1治疗反应的生物标志物，但其临床意义尚不清楚。已经证实，吲哚胺2,3-双加氧酶（IDO）的高表达与黑色素瘤抗ctla -4治疗的反应相关。然而，IDO表达是否与晚期黑色素瘤患者对抗pd -1治疗的反应相关尚不清楚。此外，在亚洲所有黑色素瘤中占很大比例的肢端和粘膜黑色素瘤与皮肤黑色素瘤在基因上是不同的亚型；然而，由于其在西方国家的发病率较低，因此尚未进行独立分析。为了评估肢端和粘膜黑色素瘤患者IDO和PD-L1表达与抗pd -1抗体应答的关系，我们采用免疫组化（IHC）方法从IDO和PD-L1表达水平的角度分析了32例经抗pd -1抗体治疗的日本肢端和粘膜黑色素瘤患者。多因素Cox回归模型显示，肿瘤中IDO低表达与无进展生存期差相关（HR = 0.33, 95% CI = 0.13-0.81, P = 0.016），而肿瘤中PD-L1表达与无进展生存期无相关性。与应答者相比，无应答者的IDO在肿瘤中的表达明显降低。评估IDO表达可能有助于在肢端和粘膜黑色素瘤患者中确定合适的抗pd -1治疗候选者。需要进一步的验证研究来评估我们研究结果的临床应用价值。
Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti-programmed death ligand-1 (PD-L1) is a well-studied biomarker for response to anti-programmed death-1 PD-1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3-dioxygenase (IDO) is correlated to a response to anti-CTLA-4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti-PD-1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD-L1 expression with response to anti-PD-1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti-PD-1 antibody from the perspective of IDO and PD-L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression-free survival (HR = 0.33, 95% CI = 0.13-0.81, P = 0.016), whereas PD-L1 expression on tumors was not associated with progression-free survival. Significantly lower expression of IDO in tumors was found in non-responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti-PD-1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings.