Macrophage targeting: opening new possibilities for cancer immunotherapy.
Macrophage targeting: opening new possibilities for cancer immunotherapy.
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DOI：
10.1111/imm.12976
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发表时间：
2018-11
期刊：
影响因子：
6.4
通讯作者：
Kitamura T
中科院分区：
文献类型：
--
作者：
Cassetta L;Kitamura T
肿瘤浸润免疫细胞负或正调节肿瘤的发生和进展。例如，细胞毒性淋巴细胞（CTL）如CD 8 + T和自然杀伤（NK）细胞可以识别和消除癌细胞，从而限制肿瘤生长和转移，如果它们发挥全部细胞毒性的话。相比之下，肿瘤浸润性骨髓细胞如肿瘤相关巨噬细胞（TAM）根据其功能状态促进癌细胞的扩增和扩散。鉴于CTL的肿瘤杀伤能力，CTL诱导的抗肿瘤免疫反应的增强被认为是致死性实体瘤的有吸引力的治疗方式，并且已经出现了几种有前途的策略，包括免疫检查点抑制剂，癌症疫苗和过继性CTL转移。这些免疫疗法目前正在临床试验中进行测试，并在淋巴瘤和一些实体瘤（如黑色素瘤和肺癌）患者中显示出显着的抗肿瘤效果。尽管有这些令人鼓舞的结果，但这些疗法在一定比例的患者和肿瘤类型中并不有效，这些患者和肿瘤类型具有肿瘤细胞内在机制，如抗原呈递受损和/或肿瘤细胞外在机制，包括免疫抑制细胞的蓄积。一些动物研究表明，肿瘤浸润性骨髓细胞，特别是TAM，是提高免疫疗法疗效的关键靶点之一，因为这些细胞可以抑制CD 8 + T和NK细胞的功能。在这篇综述中，我们将总结最近关于TAM参与免疫检查点、癌症疫苗接种和过继性CTL转移疗法的动物研究，并讨论TAM靶向改善免疫疗法的治疗潜力。
Tumour‐infiltrating immune cells regulate tumour development and progression either negatively or positively. For example, cytotoxic lymphocytes (CTL) such as CD8+ T and natural killer (NK) cells can recognize and eliminate cancer cells, and thereby restrict the tumour growth and metastasis, if they exert full cytotoxicity. In contrast, tumour‐infiltrating myeloid cells such as tumour‐associated macrophages (TAM) promote the expansion and dissemination of cancer cells depending on their functional states. Given the tumour‐killing ability of CTL, the augmentation of CTL‐induced antitumour immune reactions has been considered as an attractive therapeutic modality for lethal solid tumours and several promising strategies have emerged, which include immune checkpoint inhibitors, cancer vaccines and adoptive CTL transfer. These immunotherapies are now tested in clinical trials and have shown significant antitumour effects in patients with lymphoma and some solid tumours such as melanoma and lung cancer. Despite these encouraging results, these therapies are not efficient in a certain fraction of patients and tumour types with tumour cell‐intrinsic mechanisms such as impaired antigen presentation and/or tumour cell‐extrinsic mechanisms including the accumulation of immunosuppressive cells. Several animal studies suggest that tumour‐infiltrating myeloid cells, especially TAM, are one of the key targets to improve the efficacy of immunotherapies as these cells can suppress the functions of CD8+ T and NK cells. In this review, we will summarize recent animal studies regarding the involvement of TAM in the immune checkpoint, cancer vaccination and adoptive CTL transfer therapies, and discuss the therapeutic potential of TAM targeting to improve the immunotherapies.
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影响因子：
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作者：
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