The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Notch Signaling Determines the M1 versus M2 Polarization of Macrophages in Antitumor Immune Responses
Abstract
Macrophages are important tumor-infiltrating cells and play pivotal roles in tumor growth and metastasis. Macrophages participate in immune responses to tumors in a polarized manner: classic M1 macrophages produce interleukin (IL) 12 to promote tumoricidal responses, whereas M2 macrophages produce IL10 and help tumor progression. The mechanisms governing macrophage polarization are unclear. Here, we show that the M2-like tumor-associated macrophages (TAM) have a lower level of Notch pathway activation in mouse tumor models. Forced activation of Notch signaling increased M1 macrophages which produce IL12, no matter whether M1 or M2 inducers were applied. When Notch signaling was blocked, the M1 inducers induced M2 response in the expense of M1. Macrophages deficient in canonical Notch signaling showed TAM phenotypes. Forced activation of Notch signaling in macrophages enhanced their antitumor capacity. We further show that RBP-J–mediated Notch signaling regulates the M1 versus M2 polarization through SOCS3. Therefore, Notch signaling plays critical roles in the determination of M1 versus M2 polarization of macrophages, and compromised Notch pathway activation will lead to the M2-like TAMs. These results provide new insights into the molecular mechanisms of macrophage polarization and shed light on new therapies for cancers through the modulation of macrophage polarization through the Notch signaling. Cancer Res; 70(12); 4840–9. ©2010 AACR.
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Citations
Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
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Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190
M-1/M-2 Macrophages and the Th1/Th2 Paradigm
Mills, C. D., Kincaid, K., Alt, J. M., Heilman, M. J., & Hill, A. M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.12.6166 · Cited by 3,287
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Macrophage polarization in tumour progression
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Biochemical and functional characterization of three activated macrophage populations
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Cited by
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
Hu, X., Li, P., Guo, Y., Wang, H., Leak, R. K., Chen, S., Gao, Y., & Chen, J. (2012) · Stroke · doi:10.1161/strokeaha.112.659656 · Cited by 1,535
Self-citationNotch signaling pathway: architecture, disease, and therapeutics
Zhou, B., Lin, W., Long, Y., Yang, Y., Zhang, H., Wu, K., & Chu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00934-y · Cited by 1,114
In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment
Chen, Q., Wang, C., Zhang, X., Chen, G., Hu, Q., Li, H., Wang, J., Wen, D., Zhang, Y., Lu, Y., et al. (2019) · Nature Nanotechnology · doi:10.1038/s41565-018-0319-4 · Cited by 1,010
The complex role of tumor-infiltrating macrophages
Christofides, A., Strauss, L., Yeo, A., Cao, C., Charest, A., & Boussiotis, V. A. (2022) · Nature Immunology · doi:10.1038/s41590-022-01267-2 · Cited by 849
Metadata
- Authors
- Wang, Y.-C., He, F., Feng, F., Liu, X.-W., Dong, G.-Y., Qin, H.-Y., Hu, X.-B., Zheng, M.-H., Liang, L., Feng, L., Liang, Y.-M., & Han, H.
- Venue
- Cancer Research
- Published
- 2010-06-14
- Volume
- 70
- Issue
- 12
- Pages
- 4840-4849
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2103412440
- Cited by
- 475
- References
- 11
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wang, Y.-C., He, F., Feng, F., Liu, X.-W., Dong, G.-Y., Qin, H.-Y., Hu, X.-B., Zheng, M.-H., Liang, L., Feng, L., Liang, Y.-M., & Han, H. (2010). Notch Signaling Determines the M1 versus M2 Polarization of Macrophages in Antitumor Immune Responses. Cancer Research. https://doi.org/10.1158/0008-5472.can-10-0269
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