Tumor-associated CD19$^+$ macrophages induce immunosuppressive microenvironment in hepatocellular carcinoma
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arXiv
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| Autori principali: | , , , , , , , , , , , , , , , , , , , |
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| Natura: | Preprint |
| Pubblicazione: |
2025
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| _version_ | 1866913753532989440 |
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| author | Wang, Junli Cao, Wanyue Huang, Jinyan Zhou, Yu Zheng, Rujia Lou, Yu Yang, Jiaqi Tang, Jianghui Ye, Mao Hong, Zhengtao Wu, Jiangchao Ding, Haonan Zhang, Yuquan Sheng, Jianpeng Lu, Xinjiang Xu, Pinglong Lu, Xiongbin Bai, Xueli Liang, Tingbo Zhang, Qi |
| author_facet | Wang, Junli Cao, Wanyue Huang, Jinyan Zhou, Yu Zheng, Rujia Lou, Yu Yang, Jiaqi Tang, Jianghui Ye, Mao Hong, Zhengtao Wu, Jiangchao Ding, Haonan Zhang, Yuquan Sheng, Jianpeng Lu, Xinjiang Xu, Pinglong Lu, Xiongbin Bai, Xueli Liang, Tingbo Zhang, Qi |
| contents | Tumor-associated macrophages are a key component that contributes to the immunosuppressive microenvironment in human cancers. However, therapeutic targeting of macrophages has been a challenge in clinic due to the limited understanding of their heterogeneous subpopulations and distinct functions. Here, we identify a unique and clinically relevant CD19$^+$ subpopulation of macrophages that is enriched in many types of cancer, particularly in hepatocellular carcinoma (HCC). The CD19$^+$ macrophages exhibit increased levels of PD-L1 and CD73, enhanced mitochondrial oxidation, and compromised phagocytosis, indicating their immunosuppressive functions. Targeting CD19$^+$ macrophages with anti-CD19 chimeric antigen receptor T (CAR-T) cells inhibited HCC tumor growth. We identify PAX5 as a primary driver of up-regulated mitochondrial biogenesis in CD19$^+$ macrophages, which depletes cytoplasmic Ca$^{2+}$, leading to lysosomal deficiency and consequent accumulation of CD73 and PD-L1. Inhibiting CD73 or mitochondrial oxidation enhanced the efficacy of immune checkpoint blockade therapy in treating HCC, suggesting great promise for CD19$^+$ macrophage-targeting therapeutics. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2503_17738 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Tumor-associated CD19$^+$ macrophages induce immunosuppressive microenvironment in hepatocellular carcinoma Wang, Junli Cao, Wanyue Huang, Jinyan Zhou, Yu Zheng, Rujia Lou, Yu Yang, Jiaqi Tang, Jianghui Ye, Mao Hong, Zhengtao Wu, Jiangchao Ding, Haonan Zhang, Yuquan Sheng, Jianpeng Lu, Xinjiang Xu, Pinglong Lu, Xiongbin Bai, Xueli Liang, Tingbo Zhang, Qi Cell Behavior Tumor-associated macrophages are a key component that contributes to the immunosuppressive microenvironment in human cancers. However, therapeutic targeting of macrophages has been a challenge in clinic due to the limited understanding of their heterogeneous subpopulations and distinct functions. Here, we identify a unique and clinically relevant CD19$^+$ subpopulation of macrophages that is enriched in many types of cancer, particularly in hepatocellular carcinoma (HCC). The CD19$^+$ macrophages exhibit increased levels of PD-L1 and CD73, enhanced mitochondrial oxidation, and compromised phagocytosis, indicating their immunosuppressive functions. Targeting CD19$^+$ macrophages with anti-CD19 chimeric antigen receptor T (CAR-T) cells inhibited HCC tumor growth. We identify PAX5 as a primary driver of up-regulated mitochondrial biogenesis in CD19$^+$ macrophages, which depletes cytoplasmic Ca$^{2+}$, leading to lysosomal deficiency and consequent accumulation of CD73 and PD-L1. Inhibiting CD73 or mitochondrial oxidation enhanced the efficacy of immune checkpoint blockade therapy in treating HCC, suggesting great promise for CD19$^+$ macrophage-targeting therapeutics. |
| title | Tumor-associated CD19$^+$ macrophages induce immunosuppressive microenvironment in hepatocellular carcinoma |
| topic | Cell Behavior |
| url | https://arxiv.org/abs/2503.17738 |