Ccl22, a chemokine, is predominately produced by dendritic cells (DCs). It plays a crucial role in regulating T cell immunity via binding to its receptor CCR4, and is involved in the recruitment of regulatory T cells (Tregs) to the tumor tissue, promoting DC-Treg contacts in the lymph node [1]. In the context of cancer, targeting the CCL22-CCR4 axis may be a promising strategy for immunotherapy [1].

In animal models, when CCL22 and CCL17 were ablated in B cells, germinal centers (GCs) formed but B cells were not affinity-matured efficiently. B cells lacking CCL22 and CCL17 received less T cell help to maintain GC participation or develop into bone-marrow plasma cells, indicating CCL22's role in antibody affinity maturation in GCs [4]. In another study, injection of M2 macrophages or macrophage-derived CCL22 into inguinal white adipose tissue (iWAT) restored cold-induced beiging after local lymph node (LN) removal, and CCL22 injection promoted iWAT beiging while antibody-blocking CCL22 prevented it. The CCL22-CCR4 axis was identified as essential for LN-controlled adaptive thermogenesis [2]. In esophageal squamous cell carcinoma (ESCC), TAMs-secreted CCL22 conferred cisplatin resistance of ESCC cells and induced FAK addiction in cancer cells, and targeting DGKα enhanced the chemosensitivity of cisplatin in ESCC treatment [3,5].

In conclusion, Ccl22 is essential for various biological processes, including immune regulation, antibody affinity maturation, and adaptive thermogenesis. In disease areas such as cancer, especially ESCC, studies on Ccl22 using gene-knockout or conditional-knockout models have revealed its role in drug resistance and tumor progression, providing potential therapeutic targets.

References:

1. Röhrle, Natascha, Knott, Max M L, Anz, David. . CCL22 Signaling in the Tumor Environment. In Advances in experimental medicine and biology, 1231, 79-96. doi:10.1007/978-3-030-36667-4_8. https://pubmed.ncbi.nlm.nih.gov/32060848/

2. Yuan, Yexian, Hu, Ruoci, Park, Jooman, Shu, Gang, Jiang, Yuwei. 2024. Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure. In Science advances, 10, eadn5229. doi:10.1126/sciadv.adn5229. https://pubmed.ncbi.nlm.nih.gov/38924414/

3. Chen, Jie, Zhao, Di, Zhang, Lingyuan, Wang, Yan, Zhan, Qimin. 2024. Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase α (DGKα)/NOX4 axis. In Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 73, 101055. doi:10.1016/j.drup.2024.101055. https://pubmed.ncbi.nlm.nih.gov/38387281/

4. Liu, Bo, Lin, Yihan, Yan, Jiacong, Zhang, Luo, Qi, Hai. 2021. Affinity-coupled CCL22 promotes positive selection in germinal centres. In Nature, 592, 133-137. doi:10.1038/s41586-021-03239-2. https://pubmed.ncbi.nlm.nih.gov/33597749/

5. Chen, Jie, Zhao, Di, Zhang, Lingyuan, Wang, Yan, Zhan, Qimin. 2022. Tumor-associated macrophage (TAM)-derived CCL22 induces FAK addiction in esophageal squamous cell carcinoma (ESCC). In Cellular & molecular immunology, 19, 1054-1066. doi:10.1038/s41423-022-00903-z. https://pubmed.ncbi.nlm.nih.gov/35962191/