Enhanced IL-34 expression in Nivolumab-resistant metastatic melanoma.
Enhanced IL-34 expression in Nivolumab-resistant metastatic melanoma.
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DOI：
10.1186/s41232-018-0060-2
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发表时间：
2018
影响因子：
8.1
通讯作者：
Seino KI
中科院分区：
文献类型：
--
作者：
Han N;Baghdadi M;Ishikawa K;Endo H;Kobayashi T;Wada H;Imafuku K;Hata H;Seino KI
靶向免疫检查点分子（如PD-1）的免疫疗法有助于在黑色素瘤治疗中实现持久的反应。然而，25%对PD-1阻断表现出客观反应的黑色素瘤患者出现耐药性，并遭受疾病进展和最终死亡，这需要确定相关的耐药机制。IL-34是一种细胞因子，通过与CSF-1 R结合来控制骨髓细胞谱系的生物学。IL-34在多种疾病的发病机制中起重要作用。在癌症中，IL-34的表达被认为与肿瘤生长、转移、血管生成和治疗耐药性（例如肺癌和恶性胸膜间皮瘤）有关。在这项研究中，我们评估了IL-34在免疫抵抗中的可能参与。黑色素瘤切除标本取自一名因Nivolumab免疫治疗而患上难治性黑色素瘤的患者，并用抗IL-34、抗黑色素瘤抗原和抗CD 163抗体染色。在原发性或转移性难治性黑素瘤组织之间比较这些标记物的染色。黑色素瘤组织的免疫组织化学染色显示，与原发性黑色素瘤组织相比，转移性难治性黑色素瘤中IL-34的表达增强，这与CD 163+巨噬细胞的频率增加相关。我们首次介绍了一例转移性难治性黑色素瘤患者的临床病例，该患者获得了抗PD-1免疫治疗的耐药性，显示了IL-34在难治性黑色素瘤组织中的表达增强。
Immunotherapies that target immune-checkpoint molecules such PD-1 have helped to achieve durable responses in melanoma treatment. However, 25% of melanoma patients who showed objective responses to PD-1 blockade develop resistance and suffer from disease progression and ultimately death, which necessitates the identification of related resistance mechanisms. IL-34 is a cytokine that controls the biology of myeloid cell lineage through binding to CSF-1R. IL-34 is importantly involved in the pathogenesis of various diseases. In cancer, the expression of IL-34 has been suggested to associate with tumor growth, metastasis, angiogenesis, and therapeutic resistance such as in lung cancers and malignant pleural mesotheliomas. In this study, we evaluate the possible involvement of IL-34 in immunotherapeutic resistance. Melanoma resection species were obtained from a patient who developed a refractory melanoma against immunotherapy with Nivolumab, and stained with anti-IL-34, anti-melanoma antigens and anti-CD163 antibody. Staining of these markers was compared between primary or metastatic refractory melanoma tissues. Immunohistochemistry staining of melanoma tissues showed an enhanced expression of IL-34 in metastatic refractory melanoma compared to primary melanoma tissues, which correlates with increased frequencies of CD163+ macrophages. We introduce for the first time a clinical case of a patient with metastatic refractory melanoma that acquired resistance to anti-PD-1 immunotherapy, showing an enhanced expression of IL-34 in refractory melanoma tissues.
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影响因子：
11.2
作者：
Dunn, GP;Sheehan, KCF;Schreiber, RD
通讯作者：
Schreiber, RD
影响因子：
9
作者：
Cioce M;Canino C;Goparaju C;Yang H;Carbone M;Pass HI
通讯作者：
Pass HI
影响因子：
56.9
作者：
Lin, Haishan;Lee, Ernestine;Williams, Lewis T.
通讯作者：
Williams, Lewis T.
影响因子：
6.4
作者：
Segaliny, Aude I.;Mohamadi, Amel;Heymann, Dominique
通讯作者：
Heymann, Dominique
影响因子：
7.3
作者：
Baud'Huin, Marc;Renault, Romain;Heymann, Dominique
通讯作者：
Heymann, Dominique