Sirpα on tumor-associated myeloid cells restrains antitumor immunity in colorectal cancer independent of its interaction with CD47
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc..
Immunosuppressive myeloid cells hinder immunotherapeutic efficacy in tumors, but the precise mechanisms remain undefined. Here, by performing single-cell RNA sequencing in colorectal cancer tissues, we found tumor-associated macrophages and granulocytic myeloid-derived suppressor cells increased most compared to their counterparts in normal tissue and displayed the highest immune-inhibitory signatures among all immunocytes. These cells exhibited significantly increased expression of immunoreceptor tyrosine-based inhibitory motif-bearing receptors, including SIRPA. Notably, Sirpa-/- mice were more resistant to tumor progression than wild-type mice. Moreover, Sirpα deficiency reprogramed the tumor microenvironment through expansion of TAM_Ccl8hi and gMDSC_H2-Q10hi subsets showing strong antitumor activity. Sirpa-/- macrophages presented strong phagocytosis and antigen presentation to enhance T cell activation and proliferation. Furthermore, Sirpa-/- macrophages facilitated T cell recruitment via Syk/Btk-dependent Ccl8 secretion. Therefore, Sirpα deficiency enhances innate and adaptive immune activation independent of expression of CD47 and Sirpα blockade could be a promising strategy to improve cancer immunotherapy efficacy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Nature cancer - 5(2024), 3 vom: 10. März, Seite 500-516 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Chunliu [VerfasserIn] |
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| Anmerkungen: |
Date Completed 28.03.2024 Date Revised 28.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s43018-023-00691-z |
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| PPN (Katalog-ID): |
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| 520 | |a Immunosuppressive myeloid cells hinder immunotherapeutic efficacy in tumors, but the precise mechanisms remain undefined. Here, by performing single-cell RNA sequencing in colorectal cancer tissues, we found tumor-associated macrophages and granulocytic myeloid-derived suppressor cells increased most compared to their counterparts in normal tissue and displayed the highest immune-inhibitory signatures among all immunocytes. These cells exhibited significantly increased expression of immunoreceptor tyrosine-based inhibitory motif-bearing receptors, including SIRPA. Notably, Sirpa-/- mice were more resistant to tumor progression than wild-type mice. Moreover, Sirpα deficiency reprogramed the tumor microenvironment through expansion of TAM_Ccl8hi and gMDSC_H2-Q10hi subsets showing strong antitumor activity. Sirpa-/- macrophages presented strong phagocytosis and antigen presentation to enhance T cell activation and proliferation. Furthermore, Sirpa-/- macrophages facilitated T cell recruitment via Syk/Btk-dependent Ccl8 secretion. Therefore, Sirpα deficiency enhances innate and adaptive immune activation independent of expression of CD47 and Sirpα blockade could be a promising strategy to improve cancer immunotherapy efficacy | ||
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| 700 | 1 | |a Wang, Yingzhao |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Yongyi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiumei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Peidong |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Chengzhou |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lixiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Weibin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shoudeng |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Ni |e verfasserin |4 aut | |
| 700 | 1 | |a He, Weiling |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Wenfei |e verfasserin |4 aut | |
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