Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in Melanoma
Immunotherapy is an essential therapy for individuals with advanced melanoma. However, not all patients respond to such treatment due to individual differences. We conducted a multidimensional analysis using transcriptome data from our center, as well as publicly available databases. We found that e...
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/5/908 |
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| author | Gengpu Zhang Shengnan Li Wanyi Xiao Chao Zhang Ting Li Zhichao Liao Haotian Liu Ruwei Xing Wei Yao Jilong Yang |
| author_facet | Gengpu Zhang Shengnan Li Wanyi Xiao Chao Zhang Ting Li Zhichao Liao Haotian Liu Ruwei Xing Wei Yao Jilong Yang |
| author_sort | Gengpu Zhang |
| collection | DOAJ |
| description | Immunotherapy is an essential therapy for individuals with advanced melanoma. However, not all patients respond to such treatment due to individual differences. We conducted a multidimensional analysis using transcriptome data from our center, as well as publicly available databases. We found that effective nivolumab treatment led to an upregulation of C2 levels, and higher levels following treatment are indicative of a good outcome. Through bioinformatics analyses and immunofluorescence, we identified a correlation between C2 and M1 macrophages. To further investigate the role of C2 in melanoma, we constructed subcutaneous tumorigenic models in C57BL/6 mice. The tumors in the C2 overexpression group exhibited significantly smaller sizes. Flow cytometric analysis of the mouse tumors demonstrated enhanced recruitment of macrophages, particularly of the M1 subtype, in the overexpression group. Moreover, single-cell RNA sequencing analysis revealed that C2-positive tumor cells exhibited enhanced communication with immune cells. We co-cultured tumor cell supernatants with macrophages in vitro and observed the induction of M1 subtype polarization. In addition, we discovered a close correlation between C2 and tertiary lymphoid structures. C2 has been demonstrated to exert a protective effect, mediated by its ability to modulate the tumor microenvironment. C2 serves as a prognostic marker for melanoma and can be employed to monitor the efficacy of immunotherapy. |
| first_indexed | 2024-04-25T00:33:34Z |
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| id | doaj.art-9f7ea4424ae84dc7b82ed5b2a567ecd1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-25T00:33:34Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
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| series | Cancers |
| spelling | doaj.art-9f7ea4424ae84dc7b82ed5b2a567ecd12024-03-12T16:40:48ZengMDPI AGCancers2072-66942024-02-0116590810.3390/cancers16050908Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in MelanomaGengpu Zhang0Shengnan Li1Wanyi Xiao2Chao Zhang3Ting Li4Zhichao Liao5Haotian Liu6Ruwei Xing7Wei Yao8Jilong Yang9Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Oncology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai 519000, ChinaDepartment of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Oncology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai 519000, ChinaDepartment of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaImmunotherapy is an essential therapy for individuals with advanced melanoma. However, not all patients respond to such treatment due to individual differences. We conducted a multidimensional analysis using transcriptome data from our center, as well as publicly available databases. We found that effective nivolumab treatment led to an upregulation of C2 levels, and higher levels following treatment are indicative of a good outcome. Through bioinformatics analyses and immunofluorescence, we identified a correlation between C2 and M1 macrophages. To further investigate the role of C2 in melanoma, we constructed subcutaneous tumorigenic models in C57BL/6 mice. The tumors in the C2 overexpression group exhibited significantly smaller sizes. Flow cytometric analysis of the mouse tumors demonstrated enhanced recruitment of macrophages, particularly of the M1 subtype, in the overexpression group. Moreover, single-cell RNA sequencing analysis revealed that C2-positive tumor cells exhibited enhanced communication with immune cells. We co-cultured tumor cell supernatants with macrophages in vitro and observed the induction of M1 subtype polarization. In addition, we discovered a close correlation between C2 and tertiary lymphoid structures. C2 has been demonstrated to exert a protective effect, mediated by its ability to modulate the tumor microenvironment. C2 serves as a prognostic marker for melanoma and can be employed to monitor the efficacy of immunotherapy.https://www.mdpi.com/2072-6694/16/5/908melanomacomplement C2macrophagetertiary lymphoid structurestumor microenvironment |
| spellingShingle | Gengpu Zhang Shengnan Li Wanyi Xiao Chao Zhang Ting Li Zhichao Liao Haotian Liu Ruwei Xing Wei Yao Jilong Yang Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in Melanoma Cancers melanoma complement C2 macrophage tertiary lymphoid structures tumor microenvironment |
| title | Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in Melanoma |
| title_full | Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in Melanoma |
| title_fullStr | Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in Melanoma |
| title_full_unstemmed | Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in Melanoma |
| title_short | Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in Melanoma |
| title_sort | tumoral c2 regulates the tumor microenvironment by increasing the ratio of m1 m2 macrophages and tertiary lymphoid structures to improve prognosis in melanoma |
| topic | melanoma complement C2 macrophage tertiary lymphoid structures tumor microenvironment |
| url | https://www.mdpi.com/2072-6694/16/5/908 |
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