免疫抑制因子在肿瘤诊断与治疗中的临床应用

Hiroyasu Ito
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引用次数: 0

摘要

在癌症免疫治疗中,有两种主要的癌症治疗策略:使用免疫系统调节剂和抑制免疫检查点。免疫系统调节剂包括细胞因子、抗体和toll样受体(TLR)激动剂激活宿主对肿瘤的免疫反应。近年来,免疫抑制系统的各种机制得到了广泛的研究。免疫检查点是参与免疫抑制系统和各种癌症进展的分子。在荷瘤动物中,一些免疫检查点的表达增加,许多肿瘤通过这些免疫检查点免受宿主免疫系统的攻击。因此,免疫检查点抑制剂近年来在肿瘤免疫治疗中备受关注。免疫系统调节剂或免疫检查点抑制剂作为单一疗法用于抗癌。然而,免疫系统调节剂如TLR激动剂也会诱导免疫检查点。最近,我们报道了在荷瘤小鼠模型中,与单一治疗相比,免疫系统调节剂和免疫检查点抑制剂联合治疗具有更显著的抗肿瘤作用。在以前的报道中,TLR7激动剂(咪喹莫特)或α -半乳糖神经酰胺(GalCer)被用作免疫系统调节剂,在咪喹莫特或GalCer治疗癌症时,吲哚胺2,3-双加氧酶(IDO)或诱导型一氧化氮合酶的表达被抑制。这些联合疗法可以有效地诱导肿瘤抗原特异性细胞免疫反应。此外,IDO活性在临床上很好地反映了血液学恶性肿瘤的病情进展,IDO活性的测定有助于评估化疗期间的预后。因此,IDO等免疫检查点有助于开发新的癌症治疗和诊断方法。(审查)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Clinical Application of Immunosuppressive Factors in Cancer Diagnosis and Therapy].

In cancer immunotherapy, there are two major strategies for the treatment of cancers: the use of immune system modulators, and the inhibition of immune checkpoints. The immune system modulators including cytokines, antibodies, and Toll-like receptor (TLR) agonists activate the host immune response against tu- mors. Recently, the various mechanisms of immune suppressive systems have been extensively examined. Immune checkpoints are molecules involved in immune suppressive systems and the progression of various cancers. In tumor-bearing animals, the expression of some immune checkpoints increases, and many can- cers are protected from the host immune system by such immune checkpoints. Therefore, immune check- point inhibitors have recently been drawing much attention in cancer immunotherapy. Immune system modulators or immune checkpoint inhibitors are used against cancers as monotherapy. However, immune system modulators such as TLR agonists also induce immune checkpoints. Recently, we reported that combination therapies with immune system modulators and immune checkpoint inhibitors had more marked anti-tumor effects compared with monotherapies in a tumor-bearing mouse model. In previous reports, TLR7 agonist (imiquimod) or alpha-galactosylceramide (GalCer) was used as an immune system modulator, and the expression of indoleamine 2,3-dioxygenase (IDO) or inducible nitric oxide synthase was inhibited in cancer therapies with imiquimod or GalCer. These combination therapies can potently induce the tumor- antigen-specific cellular immune response. Moreover, the IDO activity well reflects the disease progression of hematological malignancy clinically, and the measurement of IDO activity is useful to assess the prognosis during chemotherapies. Thus, immune checkpoints such as IDO are helpful for the development of new cancer therapies and diagnosis. [Review].

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