The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors
As a practical local therapeutic approach to destroy tumor tissue, thermal ablation can activate tumor-specific T cells via enhancing tumor antigen presentation to the immune system. In the present study, we investigated changes in infiltrating immune cells in tumor tissues from the non-radiofrequen...
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MDPI AG
2023-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/5/1427 |
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| author | Wenlu Xiao Hao Huang Panpan Zheng Yingting Liu Yaping Chen Junjun Chen Xiao Zheng Lujun Chen Jingting Jiang |
| author_facet | Wenlu Xiao Hao Huang Panpan Zheng Yingting Liu Yaping Chen Junjun Chen Xiao Zheng Lujun Chen Jingting Jiang |
| author_sort | Wenlu Xiao |
| collection | DOAJ |
| description | As a practical local therapeutic approach to destroy tumor tissue, thermal ablation can activate tumor-specific T cells via enhancing tumor antigen presentation to the immune system. In the present study, we investigated changes in infiltrating immune cells in tumor tissues from the non-radiofrequency ablation (RFA) side by analyzing single-cell RNA sequencing (scRNA-seq) data of tumor-bearing mice compared with control tumors. We showed that ablation treatment could increase the proportion of CD8<sup>+</sup>T cells and the interaction between macrophages and T cells was altered. Another thermal ablation treatment, microwave ablation (MWA), increased the enrichment of signaling pathways for chemotaxis and chemokine response and was associated with the chemokine CXCL10. In addition, the immune checkpoint PD-1 was especially up-regulated in the infiltrating T cells of tumors on the non-ablation side after thermal ablation treatment. Combination therapy of ablation and PD-1 blockade had a synergistic anti-tumor effect. Furthermore, we found that the CXCL10/CXCR3 axis contributed to the therapeutic efficacy of ablation combined with anti-PD-1 therapy, and activation of the CXCL10/CXCR3 signaling pathway might improve the synergistic effect of this combination treatment against solid tumors. |
| first_indexed | 2024-03-11T07:29:52Z |
| format | Article |
| id | doaj.art-8a67e6ba9eeb4786ae8a0dd71af350de |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T07:29:52Z |
| publishDate | 2023-02-01 |
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| series | Cancers |
| spelling | doaj.art-8a67e6ba9eeb4786ae8a0dd71af350de2023-11-17T07:23:57ZengMDPI AGCancers2072-66942023-02-01155142710.3390/cancers15051427The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against TumorsWenlu Xiao0Hao Huang1Panpan Zheng2Yingting Liu3Yaping Chen4Junjun Chen5Xiao Zheng6Lujun Chen7Jingting Jiang8Department of Tumor Biological Treatment, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, ChinaDepartment of Tumor Biological Treatment, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, ChinaDepartment of Tumor Biological Treatment, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, ChinaDepartment of Tumor Biological Treatment, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, ChinaDepartment of Tumor Biological Treatment, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, ChinaDepartment of Tumor Biological Treatment, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, ChinaDepartment of Tumor Biological Treatment, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, ChinaDepartment of Tumor Biological Treatment, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, ChinaDepartment of Tumor Biological Treatment, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, ChinaAs a practical local therapeutic approach to destroy tumor tissue, thermal ablation can activate tumor-specific T cells via enhancing tumor antigen presentation to the immune system. In the present study, we investigated changes in infiltrating immune cells in tumor tissues from the non-radiofrequency ablation (RFA) side by analyzing single-cell RNA sequencing (scRNA-seq) data of tumor-bearing mice compared with control tumors. We showed that ablation treatment could increase the proportion of CD8<sup>+</sup>T cells and the interaction between macrophages and T cells was altered. Another thermal ablation treatment, microwave ablation (MWA), increased the enrichment of signaling pathways for chemotaxis and chemokine response and was associated with the chemokine CXCL10. In addition, the immune checkpoint PD-1 was especially up-regulated in the infiltrating T cells of tumors on the non-ablation side after thermal ablation treatment. Combination therapy of ablation and PD-1 blockade had a synergistic anti-tumor effect. Furthermore, we found that the CXCL10/CXCR3 axis contributed to the therapeutic efficacy of ablation combined with anti-PD-1 therapy, and activation of the CXCL10/CXCR3 signaling pathway might improve the synergistic effect of this combination treatment against solid tumors.https://www.mdpi.com/2072-6694/15/5/1427thermal ablationmicrowave ablationCXCL10tumor microenvironmentcancer immunotherapy |
| spellingShingle | Wenlu Xiao Hao Huang Panpan Zheng Yingting Liu Yaping Chen Junjun Chen Xiao Zheng Lujun Chen Jingting Jiang The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors Cancers thermal ablation microwave ablation CXCL10 tumor microenvironment cancer immunotherapy |
| title | The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors |
| title_full | The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors |
| title_fullStr | The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors |
| title_full_unstemmed | The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors |
| title_short | The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors |
| title_sort | cxcl10 cxcr3 pathway contributes to the synergy of thermal ablation and pd 1 blockade therapy against tumors |
| topic | thermal ablation microwave ablation CXCL10 tumor microenvironment cancer immunotherapy |
| url | https://www.mdpi.com/2072-6694/15/5/1427 |
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