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靶向肿瘤相关巨噬细胞作为增强免疫检查点抑制剂反应的潜在策略。

Targeting Tumor-Associated Macrophages as a Potential Strategy to Enhance the Response to Immune Checkpoint Inhibitors.

作者信息

Cassetta Luca, Kitamura Takanori

机构信息

Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, Edinburgh, United Kingdom.

Royal (Dick) School of Veterinary Studies and the Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.

出版信息

Front Cell Dev Biol. 2018 Apr 4;6:38. doi: 10.3389/fcell.2018.00038. eCollection 2018.

Abstract

Inhibition of immune checkpoint pathways in CD8 T cell is a promising therapeutic strategy for the treatment of solid tumors that has shown significant anti-tumor effects and is now approved by the FDA to treat patients with melanoma and lung cancer. However the response to this therapy is limited to a certain fraction of patients and tumor types, for reasons still unknown. To ensure success of this treatment, CD8 T cells, the main target of the checkpoint inhibitors, should exert full cytotoxicity against tumor cells. However recent studies show that tumor-associated macrophages (TAM) can impede this process by different mechanisms. In this mini-review we will summarize recent studies showing the effect of TAM targeting on immune checkpoint inhibitors efficacy. We will also discuss on the limitations of the current strategies as well on the future scientific challenges for the progress of the tumor immunology field.

摘要

抑制CD8 T细胞中的免疫检查点通路是一种很有前景的实体瘤治疗策略,已显示出显著的抗肿瘤效果,目前已获美国食品药品监督管理局(FDA)批准用于治疗黑色素瘤和肺癌患者。然而,这种疗法的反应仅限于一定比例的患者和肿瘤类型,原因尚不清楚。为确保这种治疗的成功,检查点抑制剂的主要靶点CD8 T细胞应发挥对肿瘤细胞的完全细胞毒性。然而,最近的研究表明,肿瘤相关巨噬细胞(TAM)可通过不同机制阻碍这一过程。在本综述中,我们将总结最近的研究,这些研究显示了靶向TAM对免疫检查点抑制剂疗效的影响。我们还将讨论当前策略的局限性以及肿瘤免疫学领域进展面临的未来科学挑战。

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