ANKRD22 participates in the proinflammatory activities of macrophages in the colon cancer tumor microenvironment
Abstract Tumor-associated macrophages (TAMs) are among the most common types of immune cells in the colon cancer microenvironment. Reprogramming M2-type TAMs with immunosuppressive functions into M1-type TAMs with proinflammatory functions is a novel strategy for reshaping the tumor microenvironment...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03930-z |
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| author | Xiaoying Wang Keqing Yang Bin Yang Rui Wang Yongliang Zhu Tianhui Pan |
| author_facet | Xiaoying Wang Keqing Yang Bin Yang Rui Wang Yongliang Zhu Tianhui Pan |
| author_sort | Xiaoying Wang |
| collection | DOAJ |
| description | Abstract Tumor-associated macrophages (TAMs) are among the most common types of immune cells in the colon cancer microenvironment. Reprogramming M2-type TAMs with immunosuppressive functions into M1-type TAMs with proinflammatory functions is a novel strategy for reshaping the tumor microenvironment (TME) and enhancing the efficacy of immunotherapy in colon cancer. However, the key molecules and mechanisms underlying TAM polarization require further clarification. Our previous study suggested that ANKRD22 may play a role in regulating the functional state transition of macrophages. However, the expression levels of ANKRD22 in colon TAMs and its specific effects on tumor proliferation remain unclear. In the present study, we observed elevated ANKRD22 expression in M1-type TAMs. The expression level of ANKRD22 was positively correlated with the survival period of patients with colon cancer and with the infiltration abundance of M1-type TAMs, and ANKRD22 expression was negatively correlated with the infiltration abundance of M2-type TAMs. A significant decrease in ANKRD22 expression in macrophages cocultured with colon cancer cell culture supernatant as well as in macrophages directly derived from colorectal cancer tissues was observed. Single-cell RNA sequencing, spatial transcriptomic studies, and subcutaneous xenograft experiments in mice revealed that Ankrd22 silencing altered the subtype distribution of macrophages, attenuated their proinflammatory activity, and enhanced their protumor activity. Additionally, we identified a small-molecule ANKRD22 upregulator that could aid in the development of novel therapeutics targeting TAM remodeling. |
| format | Article |
| id | doaj-art-d8d3c8fc12d443caa177b0a749fa5137 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-d8d3c8fc12d443caa177b0a749fa51372025-02-02T12:26:29ZengSpringerCancer Immunology, Immunotherapy1432-08512025-02-0174311410.1007/s00262-024-03930-zANKRD22 participates in the proinflammatory activities of macrophages in the colon cancer tumor microenvironmentXiaoying Wang0Keqing Yang1Bin Yang2Rui Wang3Yongliang Zhu4Tianhui Pan5Laboratory of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of MedicineInternal Medicine, Guizhou Provincial People’s HospitalLaboratory of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of MedicineLaboratory of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of MedicineLaboratory of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of MedicineLaboratory of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of MedicineAbstract Tumor-associated macrophages (TAMs) are among the most common types of immune cells in the colon cancer microenvironment. Reprogramming M2-type TAMs with immunosuppressive functions into M1-type TAMs with proinflammatory functions is a novel strategy for reshaping the tumor microenvironment (TME) and enhancing the efficacy of immunotherapy in colon cancer. However, the key molecules and mechanisms underlying TAM polarization require further clarification. Our previous study suggested that ANKRD22 may play a role in regulating the functional state transition of macrophages. However, the expression levels of ANKRD22 in colon TAMs and its specific effects on tumor proliferation remain unclear. In the present study, we observed elevated ANKRD22 expression in M1-type TAMs. The expression level of ANKRD22 was positively correlated with the survival period of patients with colon cancer and with the infiltration abundance of M1-type TAMs, and ANKRD22 expression was negatively correlated with the infiltration abundance of M2-type TAMs. A significant decrease in ANKRD22 expression in macrophages cocultured with colon cancer cell culture supernatant as well as in macrophages directly derived from colorectal cancer tissues was observed. Single-cell RNA sequencing, spatial transcriptomic studies, and subcutaneous xenograft experiments in mice revealed that Ankrd22 silencing altered the subtype distribution of macrophages, attenuated their proinflammatory activity, and enhanced their protumor activity. Additionally, we identified a small-molecule ANKRD22 upregulator that could aid in the development of novel therapeutics targeting TAM remodeling.https://doi.org/10.1007/s00262-024-03930-zColon cancerTumor microenvironmentTumor-associated macrophagesANKRD22 |
| spellingShingle | Xiaoying Wang Keqing Yang Bin Yang Rui Wang Yongliang Zhu Tianhui Pan ANKRD22 participates in the proinflammatory activities of macrophages in the colon cancer tumor microenvironment Cancer Immunology, Immunotherapy Colon cancer Tumor microenvironment Tumor-associated macrophages ANKRD22 |
| title | ANKRD22 participates in the proinflammatory activities of macrophages in the colon cancer tumor microenvironment |
| title_full | ANKRD22 participates in the proinflammatory activities of macrophages in the colon cancer tumor microenvironment |
| title_fullStr | ANKRD22 participates in the proinflammatory activities of macrophages in the colon cancer tumor microenvironment |
| title_full_unstemmed | ANKRD22 participates in the proinflammatory activities of macrophages in the colon cancer tumor microenvironment |
| title_short | ANKRD22 participates in the proinflammatory activities of macrophages in the colon cancer tumor microenvironment |
| title_sort | ankrd22 participates in the proinflammatory activities of macrophages in the colon cancer tumor microenvironment |
| topic | Colon cancer Tumor microenvironment Tumor-associated macrophages ANKRD22 |
| url | https://doi.org/10.1007/s00262-024-03930-z |
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