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

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

doi:10.1038/s41586-019-1456-0

Cited by 813 publications

(923 citation statements)

References 28 publications

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“…Up to now, the TME, especially tumour associated inflammation and the interaction between tumour cell and immune cells is not very clear. It is universally accepted that glioma-secreted soluble factors and TME-secreted soluble factors all take part in the formation of the TME, and promote the proliferation of tumour cells (Barkal et al, 2019). What has been mentioned is that much research has focused on the micro-environment inside the glioma itself (Thorsson et al, 2018;Platten et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

Liu

Gao

et al. 2020

Brain, Behavior, and Immunity

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Section: Discussionmentioning

confidence: 99%

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

Liu

Gao

et al. 2020

Brain, Behavior, and Immunity

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“…9,10 Antitumor therapies based on macrophages and other innate immune cells are also in clinical trials. [11][12][13][14] Macrophages, as the first line of innate immunity, kill pathogens and cancer cells through phagocytosis. 15 Recent studies have shown that macrophages express signal regulatory protein α (Sirpα), a receptor protein that distinguishes "self" and "non-self", while normal tissue cells express the "self" ligand protein CD47.…”

Section: Introductionmentioning

confidence: 99%

The Ap-2α/Elk-1 axis regulates Sirpα-dependent tumor phagocytosis by tumor-associated macrophages in colorectal cancer

Wang

Luo

Chen

et al. 2020

Sig Transduct Target Ther

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The inhibitory receptor signal regulatory protein-α (Sirpα) is a myeloid-specific immune checkpoint that engages the "don't eat me" signal CD47, which is expressed on tumor and normal tissue cells. However, the profile and regulatory mechanism of Sirpα expression in tumor-associated macrophages (TAMs) are still not clear. Here, we found that the expression of Sirpα in TAMs increased dynamically with colorectal cancer (CRC) progression. Mechanistically, CRC cell-derived lactate induced the nuclear translocation of the transcription factor Ap-2α from the cytoplasm in TAMs. Ap-2α functioned as a transcription factor for Elk-1 by binding to the conserved element GCCTGC located at −1396/−1391 in the mouse Elk-1 promoter. Subsequently, the Elk-1 protein bound to two conserved sites, CTTCCTACA (located at −229/−221) and CTTCCTCTC (located at −190/−182), in the mouse Sirpα promoter and promoted Sirpα expression in TAMs. Functionally, the macrophage-specific knockout of Ap-2α notably promoted the phagocytic activity of TAMs and suppressed CRC progression, whereas these effects were prevented by the transgenic macrophage-specific expression of Elk-1, which regulated TAM phagocytosis and CRC development in a Sirpα-dependent manner. Furthermore, we showed that Elk-1 expression was positively correlated with Sirpα expression in TAMs and was associated with poor survival in CRC patients. Taken together, our findings revealed a novel mechanism through which CRC evades innate immune surveillance and provided potential targets for macrophage-based immunotherapy for CRC patients.Signal Transduction and Targeted Therapy (2020) 5:35; https://doi.

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“…Most recently, the Stanford team has reported the discovery of CD24 – a protein also displayed on the surface of cancer cells to signal to macrophages not to engulf them – in Nature [7]. …”

Section: Bench With Bedsidementioning

confidence: 99%

Integrative Approaches to Cancer Research

Sawyer

2019

BioTechniques

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

Cited by 813 publications

References 28 publications

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

The Ap-2α/Elk-1 axis regulates Sirpα-dependent tumor phagocytosis by tumor-associated macrophages in colorectal cancer

Integrative Approaches to Cancer Research

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