免疫反应调节在癌症治疗中具有治疗潜力

M. Festa
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摘要

背景:根据它们的分化途径,免疫细胞在肿瘤进展中可能有相反的作用。因此,在生长过程中,肿瘤承受选择性压力产生免疫抑制因子,促进肿瘤生长、血管生成和转移。本文综述了不同巨噬细胞和T细胞对肿瘤进展的贡献,以及它们在当前癌症免疫治疗中的作用。方法:我们通过麦吉尔图书馆在线检索文章,检索词包括不同免疫细胞的名称以及“极性”、“肿瘤进展”或“癌症免疫治疗”。癌症疗法“CTLA-4阻断”、“Ipilimumab”、“过继细胞转移”和“PD1抑制”也被用作搜索词。根据所涉及的细胞类型,肿瘤基质中不同免疫细胞之间的串扰可以促进肿瘤的发展或抑制肿瘤的生长。某些疗法,如过继细胞毒性T淋巴细胞(CTL)转移和CTLA-4和PD1抑制,通过增强CTL杀瘤反应起作用,并在一小部分但重要的患者中产生了持久的反应。其他疗法通过扭曲肿瘤相关巨噬细胞的表型从致瘤性到抗致瘤性起作用。然而,破坏免疫细胞功能之间的平衡有可能引发炎症性疾病,如自身免疫。因此,癌症免疫治疗的未来方向包括靶向潜在应答者和将治疗机制限制在肿瘤微环境。
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Immune Response Regulation has Therapeutic Potential in the Treatment of Cancer
Background: Depending on their path of differentiation, immune cells can have opposing roles in tumour progression. As a result, during growth, tumours undergo selective pressure to produce immunosuppressive factors that contribute to tumour growth, angiogenesis, and metastasis. This review discusses the contribution of different macrophages and T cells to tumour progression, as well as their role in current cancer immunotherapies. Methods: We searched for articles online through McGill Library with search terms including the names of different immune cells along with “polarity”, “tumour progression”, or “cancer immunotherapy”. Cancer therapies “CTLA-4 blockade”, “Ipilimumab”, “adoptive cell transfer”, and “PD1 inhibition” were also used as search terms. Summary: Depending on the cell types involved, crosstalk between different immune cells in the tumour stroma can contribute to either the development or the inhibition of tumour growth. Certain therapies such as adoptive cytotoxic T lymphocyte (CTLs) transfer and CTLA-4 & PD1 inhibition work by enhancing CTL tumoricidal responses, and have produced durable responses in a small but significant group of patients. Other therapies work by skewing the phenotype of tumour associated macrophages from pro-tumorigenic to anti-tumorigenic. However, disrupting the balance between immune cell functions risks triggering inflammatory disorders such as autoimmunity. Therefore, future directions in cancer immunotherapy include targeting potential responders and restricting therapeutic mechanisms to the tumour microenvironment.
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