Ccl22, a chemokine, is predominately produced by dendritic cells. It regulates T cell immunity through binding to its receptor CCR4, playing a crucial role in processes like T reg migration. By recruiting T regs to tumor tissue and promoting DC-T reg contacts in lymph nodes, it influences the tumor immune microenvironment. Additionally, it may be involved in other biological processes related to immunity and cell-cell interactions [1].

In cancer, somatic mutations in Ccl22 drive the development of a distinct subset of CLPD-NK [5]. Ccl22-based peptide vaccines can modulate the tumor microenvironment, increasing the infiltration of CD8+ cells and M1 macrophages, and augmenting anti-tumor responses [6]. In esophageal squamous cell carcinoma, TAM-secreted Ccl22 confers cisplatin resistance by regulating the DGKα/NOX4 axis [3], and also induces FAK addiction, which is associated with increased cancer cell malignant progression [8]. In endometrial cancer, Ccl22 is associated with overall survival, depending on its location and the cell type producing it [9]. In adipose tissue, macrophage-derived Ccl22 promotes inguinal white adipose tissue beiging, and its levels are inversely correlated with body weight and fat mass in mice and humans [2]. In germinal centers, GC B cells upregulate Ccl22 upon CD40 stimulation, which helps attract TFH cells for antibody affinity maturation [4]. In fibroblast-like synoviocytes, Ccl22 treatment promotes a pro-inflammatory state [7].

In summary, Ccl22 is essential in regulating the immune response, especially in the context of cancer and metabolic diseases. Studies, including those potentially using KO/CKO mouse models (although not always explicitly stated), have revealed its role in processes such as tumor immune evasion, drug resistance, adipose thermogenesis, and germinal center B-cell selection, highlighting its potential as a therapeutic target in various disease areas.

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. . . CCL22 Mutations Promote NK-cell Lymphoproliferative Disease. In Cancer discovery, 12, OF17. doi:10.1158/2159-8290.CD-RW2022-088. https://pubmed.ncbi.nlm.nih.gov/35554510/

6. Lecoq, Inés, Kopp, Katharina L, Chapellier, Marion, Wakatsuki Pedersen, Ayako, Andersen, Mads Hald. 2022. CCL22-based peptide vaccines induce anti-cancer immunity by modulating tumor microenvironment. In Oncoimmunology, 11, 2115655. doi:10.1080/2162402X.2022.2115655. https://pubmed.ncbi.nlm.nih.gov/36052217/

7. Ren, Guomin, Al-Jezani, Nedaa, Railton, Pamela, Powell, James N, Krawetz, Roman J. 2020. CCL22 induces pro-inflammatory changes in fibroblast-like synoviocytes. In iScience, 24, 101943. doi:10.1016/j.isci.2020.101943. https://pubmed.ncbi.nlm.nih.gov/33490888/

8. 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/

9. Mannewitz, Mareike, Kolben, Thomas, Perleberg, Carolin, Jeschke, Udo, Beyer, Susanne. 2024. CCL22 as an independent prognostic factor in endometrial cancer patients. In Translational oncology, 50, 102116. doi:10.1016/j.tranon.2024.102116. https://pubmed.ncbi.nlm.nih.gov/39232378/