小结

系列：深度综述——癌症免疫疗法新靶点“吞噬作用检查点”

杂志：Nature Reviews Cancer

亮点：来自美国希望之城综合癌症中心等机构的6位科学家在一篇最新综述中详细介绍了过去20年在识别吞噬作用检查点（以CD47-SIRPα轴为主）方面取得的进展，以及支持在癌症治疗中使用吞噬作用检查点阻断的临床前和早期临床证据。同时，文章讨论了阻断吞噬作用检查点后调控先天和适应性抗肿瘤免疫反应的机制，并强调如何桥接免疫系统的这两个分支来是产生最佳抗肿瘤免疫力的关键。

相关论文：

[1] Mingye Feng et al. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nature Reviews Cancer (2019) .

[2] Seiffert, M. et al. Human signal-regulatory protein is expressed on normal, but not on subsets of leukemic myeloid cellsand mediates cellular adhesion involving its counterreceptor CD47. Blood (1999).

[3] Gordon, S. R. et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature(2017).

[4] Pollard, J. W. Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer (2004).

[5] Barkal, A. A. et al. Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy. Nat. Immunol. (2018).

[6] Golay, J. et al. Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab. Blood (2013).

[7] Liu, X. et al. CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nat. Med. (2015).

[8] Sockolosky, J. T. et al. Durable antitumor responses to CD47 blockade require adaptive immune stimulation. Proc. Natl Acad. Sci. (2016).

[9] Rakoff-Nahoum, S. & Medzhitov, R.Toll-like receptors and cancer. Nat. Rev. Cancer (2009).

[10] Majeti, R. et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell (2009).

[11] Willingham, S. B. et al. The CD47-signal regulatory protein alpha (SIRPα) interaction is a therapeutic target for human solid tumors. Proc. Natl Acad. Sci. (2012).

[12] Liu, J. et al. Pre-clinical development of a humanized anti-CD47 antibody with anti-cancer therapeutic potential. PLOS ONE (2015).

[13] Weiskopf, K. et al. Engineered SIRPα variants as immunotherapeutic adjuvants to anticancer antibodies. Science(2013).

[14] Lin, G. H. Y. et al. TTI-621 (SIRPαFc), a CD47-blocking cancer immunotherapeutic, triggers phagocytosis of lymphoma cells by multiple polarized macrophage subsets. PLOS ONE (2017).

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