CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy (Naturevolume 2019, 572:392-396)

報告日期: 2019/10/04
報告時間: 17:10/18:00
報告學生: 楊翔傑(英文報告)
講評老師: 張志鵬
附件下載:

CD24 signaling through macrophage Siglec-10 is a target for cancer immunotherapy

Amira A. Barkal, Rachel E. Brewer, Maxim Markovic, Mark Kowarsky, Sammy A. Barkal, Balyn W. Zaro, Venkatesh Krishnan, Jason Hatakeyama, Oliver Dorigo, Layla J. Barkal8 & Irving L. Weissman

Nature. 2019 Aug; 572(7769):392-396.

Speaker: Shiang-Jie Yang                           Time: 17:10-18:00, Oct.4, 2019

Commentator: Dr. Chih-Peng Chang           Place: Room 602

Abstract:

 Tumor microenvironment is considered to play a critical role in promoting tumor growth and drug resistance. Growing studies have also demonstrated that targeting tumor microenvironment is a potential strategy in cancer therapy. Cancer cells can shape the tumor microenvironment to support tumor progression via various signaling pathways, including increased infiltration of tumor-associated macrophages (TAMs). In previous studies, tumor-associated macrophages are regarded as immune suppressive immune cells that can promote tumor growth by suppressing anti-tumor immunity. However, macrophage phagocytosis plays an important role in bridging innate immunity and adoptive immunity. Therefore, cancer cells can recruit TAM and inhibit its phagocytosis to promote tumor growth. CD24, a highly glycosylated protein, is expressed on the surface of B cell, neutrophil and neuroblast. Its upregulation is associated with cancer cell development, invasion and migration. In addition, some studies revealed that CD24 can interact with Siglec10, which is expressed on innate immune cell, to reduce inflammation. However, whether CD24 plays an important role in regulating tumor immunity remains unclear. In this study, the author showed that CD24 is majorly expressed on tumor cells and SIGLEC10 is expressed on tumor-associated macrophages in tumor microenvironment. Deletion of CD24 in cancer cells or Siglect10 in macrophages leads to promote tumor-associated macrophage phagocytosis in vitro and in vivo. Blockade of CD24 with monoclonal antibody can inhibit tumor growth through enhanced macrophage phagocytosis in mice model. In summary, the author found that CD24 can act as immune checkpoint on cancer cell to inhibit phagocytosis and targeting CD24 may be a promising strategy in cancer therapy through promoting anti-tumor immunity.

Reference

1          Feng, M. et al. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nat Rev Cancer 19, 568-586, doi:10.1038/s41568-019-0183-z (2019).