{"title":"阻断CX3CR1+肿瘤相关巨噬细胞可增强肝细胞癌抗PD-1疗法的疗效","authors":"Xiaonan Xiang, Kai Wang, Hui Zhang, Haibo Mou, Zhixiong Shi, Yaoye Tao, Hongliang Song, Zhengxing Lian, Shuai Wang, Di Lu, Xuyong Wei, Haiyang Xie, Shusen Zheng, Jianguo Wang, Xiao Xu","doi":"10.1158/2326-6066.CIR-23-0627","DOIUrl":null,"url":null,"abstract":"<p><p>The efficacy of immune checkpoint inhibitors (ICI) in the treatment of hepatocellular carcinoma (HCC) remains limited, highlighting the need for further investigation into the underlying mechanisms. Accumulating evidence indicates that tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) are implicated in immune evasion and treatment resistance. This study aimed to explore the contribution of TAMs in the HCC TME. Our findings reveal the critical involvement of CX3C motif chemokine receptor 1 (CX3CR1)-positive TAMs in inducing T cell exhaustion through interleukin-27 (IL-27) secretion, providing valuable insights into the mechanisms underlying the suboptimal efficacy of anti-PD-1 therapy in HCC. Moreover, we identified prostaglandin E2 (PGE2), released by immune-attacked tumor cells, as a key regulator of CX3CR1+ TAM phenotype transition. To augment the therapeutic response to current anti-PD-1 therapy, we propose an innovative treatment strategy that incorporates targeting CX3CR1+ TAMs in addition to anti-PD-1 therapy. In conclusion, our study contributes to the understanding of TAMs' role in cancer immunotherapy and highlights potential clinical implications for HCC treatment. The combination of targeting CX3CR1+ TAMs with anti-PD-1 therapy holds promise for enhancing the efficacy of immunotherapeutic interventions in HCC patients.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":null,"pages":null},"PeriodicalIF":8.1000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Blocking CX3CR1+ Tumor-associated Macrophages Enhances the Efficacy of Anti-PD-1 Therapy in Hepatocellular Carcinoma.\",\"authors\":\"Xiaonan Xiang, Kai Wang, Hui Zhang, Haibo Mou, Zhixiong Shi, Yaoye Tao, Hongliang Song, Zhengxing Lian, Shuai Wang, Di Lu, Xuyong Wei, Haiyang Xie, Shusen Zheng, Jianguo Wang, Xiao Xu\",\"doi\":\"10.1158/2326-6066.CIR-23-0627\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The efficacy of immune checkpoint inhibitors (ICI) in the treatment of hepatocellular carcinoma (HCC) remains limited, highlighting the need for further investigation into the underlying mechanisms. Accumulating evidence indicates that tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) are implicated in immune evasion and treatment resistance. This study aimed to explore the contribution of TAMs in the HCC TME. Our findings reveal the critical involvement of CX3C motif chemokine receptor 1 (CX3CR1)-positive TAMs in inducing T cell exhaustion through interleukin-27 (IL-27) secretion, providing valuable insights into the mechanisms underlying the suboptimal efficacy of anti-PD-1 therapy in HCC. Moreover, we identified prostaglandin E2 (PGE2), released by immune-attacked tumor cells, as a key regulator of CX3CR1+ TAM phenotype transition. To augment the therapeutic response to current anti-PD-1 therapy, we propose an innovative treatment strategy that incorporates targeting CX3CR1+ TAMs in addition to anti-PD-1 therapy. In conclusion, our study contributes to the understanding of TAMs' role in cancer immunotherapy and highlights potential clinical implications for HCC treatment. The combination of targeting CX3CR1+ TAMs with anti-PD-1 therapy holds promise for enhancing the efficacy of immunotherapeutic interventions in HCC patients.</p>\",\"PeriodicalId\":9474,\"journal\":{\"name\":\"Cancer immunology research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.1000,\"publicationDate\":\"2024-08-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer immunology research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1158/2326-6066.CIR-23-0627\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer immunology research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/2326-6066.CIR-23-0627","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Blocking CX3CR1+ Tumor-associated Macrophages Enhances the Efficacy of Anti-PD-1 Therapy in Hepatocellular Carcinoma.
The efficacy of immune checkpoint inhibitors (ICI) in the treatment of hepatocellular carcinoma (HCC) remains limited, highlighting the need for further investigation into the underlying mechanisms. Accumulating evidence indicates that tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) are implicated in immune evasion and treatment resistance. This study aimed to explore the contribution of TAMs in the HCC TME. Our findings reveal the critical involvement of CX3C motif chemokine receptor 1 (CX3CR1)-positive TAMs in inducing T cell exhaustion through interleukin-27 (IL-27) secretion, providing valuable insights into the mechanisms underlying the suboptimal efficacy of anti-PD-1 therapy in HCC. Moreover, we identified prostaglandin E2 (PGE2), released by immune-attacked tumor cells, as a key regulator of CX3CR1+ TAM phenotype transition. To augment the therapeutic response to current anti-PD-1 therapy, we propose an innovative treatment strategy that incorporates targeting CX3CR1+ TAMs in addition to anti-PD-1 therapy. In conclusion, our study contributes to the understanding of TAMs' role in cancer immunotherapy and highlights potential clinical implications for HCC treatment. The combination of targeting CX3CR1+ TAMs with anti-PD-1 therapy holds promise for enhancing the efficacy of immunotherapeutic interventions in HCC patients.
期刊介绍:
Cancer Immunology Research publishes exceptional original articles showcasing significant breakthroughs across the spectrum of cancer immunology. From fundamental inquiries into host-tumor interactions to developmental therapeutics, early translational studies, and comprehensive analyses of late-stage clinical trials, the journal provides a comprehensive view of the discipline. In addition to original research, the journal features reviews and opinion pieces of broad significance, fostering cross-disciplinary collaboration within the cancer research community. Serving as a premier resource for immunology knowledge in cancer research, the journal drives deeper insights into the host-tumor relationship, potent cancer treatments, and enhanced clinical outcomes.
Key areas of interest include endogenous antitumor immunity, tumor-promoting inflammation, cancer antigens, vaccines, antibodies, cellular therapy, cytokines, immune regulation, immune suppression, immunomodulatory effects of cancer treatment, emerging technologies, and insightful clinical investigations with immunological implications.