The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Targeting the CCL2/CCR2 Axis in Cancer Immunotherapy: One Stone, Three Birds?
Open accessAbstract
CCR2 is predominantly expressed by monocytes/macrophages with strong proinflammatory functions, prompting the development of CCR2 antagonists to dampen unwanted immune responses in inflammatory and autoimmune diseases. Paradoxically, CCR2-expressing monocytes/macrophages, particularly in tumor microenvironments, can be strongly immunosuppressive. Thus, targeting the recruitment of immunosuppressive monocytes/macrophages to tumors by CCR2 antagonism has recently been investigated as a strategy to modify the tumor microenvironment and enhance anti-tumor immunity. We present here that beneficial effects of CCR2 antagonism in the tumor setting extend beyond blocking chemotaxis of suppressive myeloid cells. Signaling within the CCL2/CCR2 axis shows underappreciated effects on myeloid cell survival and function polarization. Apart from myeloid cells, T cells are also known to express CCR2. Nevertheless, tissue homing of Treg cells among T cell populations is preferentially affected by CCR2 deficiency. Further, CCR2 signaling also directly enhances Treg functional potency. Thus, although Tregs are not the sole type of T cells expressing CCR2, the net outcome of CCR2 antagonism in T cells favors the anti-tumor arm of immune responses. Finally, the CCL2/CCR2 axis directly contributes to survival/growth and invasion/metastasis of many types of tumors bearing CCR2. Together, CCR2 links to two main types of suppressive immune cells by multiple mechanisms. Such a CCR2-assoicated immunosuppressive network is further entangled with paracrine and autocrine CCR2 signaling of tumor cells. Strategies to target CCL2/CCR2 axis as cancer therapy in the view of three types of CCR2-expessing cells in tumor microenvironment are discussed.
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Targeting cytokine and chemokine signaling pathways for cancer therapy
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Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets
Guan, F., Wang, R., Yi, Z., Luo, P., Liu, W., Xie, Y., Liu, Z., Xia, Z., Zhang, H., & Cheng, Q. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02124-y · Cited by 371
Hypoxia-inducible factor orchestrates adenosine metabolism to promote liver cancer development
Cheu, J. W.-S., Chiu, D. K.-C., Kwan, K. K.-L., Yang, C., Yuen, V. W.-H., Goh, C. C., Chui, N. N.-Q., Shen, W., Law, C.-T., Li, Q., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade5111 · Cited by 65
Arfaei, R., Mikaeili, N., Daj, F., Boroumand, A., Kheyri, A., Yaraghi, P., Shirzad, Z., Keshavarz, M., Hassanshahi, G., Jafarzadeh, A., et al. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112328 · Cited by 27
Metadata
- Authors
- Fei, L., Ren, X., Yu, H., & Zhan, Y.
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2021-11-03
- Volume
- 12
- Pages
- 771210-771210
- ISSN
- 1664-3224 (ISSN-L)
- OpenAlex
- W3209605673
- Cited by
- 219
- References
- 21
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- gold
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- Fei, L., Ren, X., Yu, H., & Zhan, Y. (2021). Targeting the CCL2/CCR2 Axis in Cancer Immunotherapy: One Stone, Three Birds? Frontiers in Immunology. https://doi.org/10.3389/fimmu.2021.771210
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