Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response
Abstract Immunotherapies employing PD‐1/PD‐L1 immune checkpoint inhibitors (ICIs) are vital for primary liver cancer (PLC), but response rates remain unsatisfying. Accurate differentiation of responders from non‐responders to immunotherapy is imperative. Here, single‐cell‐scaled mass cytometry analy...
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Wiley
2024-12-01
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| Online Access: | https://doi.org/10.1002/advs.202309631 |
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| author | Jun Xue Shuai Yang Si‐Si Zhang Jun Fan Zi‐Long Wu Cheng‐Jun Sui Yong‐Qiang Yang Jin‐Feng Zhang Pian Liu De‐Jun Zhang Xin‐Yao Qiu Tao Zhang Lei Chen Gang Wu Hong‐Yang Wang Jing Tang |
| author_facet | Jun Xue Shuai Yang Si‐Si Zhang Jun Fan Zi‐Long Wu Cheng‐Jun Sui Yong‐Qiang Yang Jin‐Feng Zhang Pian Liu De‐Jun Zhang Xin‐Yao Qiu Tao Zhang Lei Chen Gang Wu Hong‐Yang Wang Jing Tang |
| author_sort | Jun Xue |
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| description | Abstract Immunotherapies employing PD‐1/PD‐L1 immune checkpoint inhibitors (ICIs) are vital for primary liver cancer (PLC), but response rates remain unsatisfying. Accurate differentiation of responders from non‐responders to immunotherapy is imperative. Here, single‐cell‐scaled mass cytometry analysis on sequential peripheral blood mononuclear cells (PBMCs) from ICI‐treated PLC patients is conducted, and tissue residence of immune subpopulations is assessed via multiplex immunohistochemistry. In the discovery cohort (n = 24), responders have lower baseline B cell and HLA‐DR+CD8+T cell, and higher CD14+CD16− classical monocyte (CM) proportions. CMs decrease more in responders PBMCs, while HLA‐DR+CD8+T cells conformably amplify after ICI‐exposure. Responsive individuals display upregulated exhaustion and activation markers in peripheral immune lineages. In the expanded cohort of 77 patients, the augment of the B cells in non‐responders is re‐confirmed. Responders demonstrate much higher enrichment of B cells or tertiary lymphoid structures in tumor compared to non‐responders. A prospective model that excelled in early discrimination of responders is developed using generalized linear model and achieves a satisfactory AUC over 0.9 in all three independent cohorts. Integratedly, the study unveils dynamic immune landscapes in PLC patients undergoing ICI‐based therapy, aiding in PLC patient stratification for ICI‐based treatment and fostering new response monitoring strategies. |
| format | Article |
| id | doaj-art-d910fc75d24e484495cf1ee35cd05758 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d910fc75d24e484495cf1ee35cd057582024-12-18T14:18:10ZengWileyAdvanced Science2198-38442024-12-011147n/an/a10.1002/advs.202309631Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy ResponseJun Xue0Shuai Yang1Si‐Si Zhang2Jun Fan3Zi‐Long Wu4Cheng‐Jun Sui5Yong‐Qiang Yang6Jin‐Feng Zhang7Pian Liu8De‐Jun Zhang9Xin‐Yao Qiu10Tao Zhang11Lei Chen12Gang Wu13Hong‐Yang Wang14Jing Tang15Cancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaFudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaThe International Cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery Hospital Naval Medical University Shanghai 200438 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaFudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaThe International Cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery Hospital Naval Medical University Shanghai 200438 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaFudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 ChinaCancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaAbstract Immunotherapies employing PD‐1/PD‐L1 immune checkpoint inhibitors (ICIs) are vital for primary liver cancer (PLC), but response rates remain unsatisfying. Accurate differentiation of responders from non‐responders to immunotherapy is imperative. Here, single‐cell‐scaled mass cytometry analysis on sequential peripheral blood mononuclear cells (PBMCs) from ICI‐treated PLC patients is conducted, and tissue residence of immune subpopulations is assessed via multiplex immunohistochemistry. In the discovery cohort (n = 24), responders have lower baseline B cell and HLA‐DR+CD8+T cell, and higher CD14+CD16− classical monocyte (CM) proportions. CMs decrease more in responders PBMCs, while HLA‐DR+CD8+T cells conformably amplify after ICI‐exposure. Responsive individuals display upregulated exhaustion and activation markers in peripheral immune lineages. In the expanded cohort of 77 patients, the augment of the B cells in non‐responders is re‐confirmed. Responders demonstrate much higher enrichment of B cells or tertiary lymphoid structures in tumor compared to non‐responders. A prospective model that excelled in early discrimination of responders is developed using generalized linear model and achieves a satisfactory AUC over 0.9 in all three independent cohorts. Integratedly, the study unveils dynamic immune landscapes in PLC patients undergoing ICI‐based therapy, aiding in PLC patient stratification for ICI‐based treatment and fostering new response monitoring strategies.https://doi.org/10.1002/advs.202309631efficacy prediction modelimmune‐checkpoint inhibition‐based therapyperipheral immune landscapesprimary liver cancer |
| spellingShingle | Jun Xue Shuai Yang Si‐Si Zhang Jun Fan Zi‐Long Wu Cheng‐Jun Sui Yong‐Qiang Yang Jin‐Feng Zhang Pian Liu De‐Jun Zhang Xin‐Yao Qiu Tao Zhang Lei Chen Gang Wu Hong‐Yang Wang Jing Tang Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response Advanced Science efficacy prediction model immune‐checkpoint inhibition‐based therapy peripheral immune landscapes primary liver cancer |
| title | Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response |
| title_full | Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response |
| title_fullStr | Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response |
| title_full_unstemmed | Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response |
| title_short | Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response |
| title_sort | deciphering the multifaceted immune landscape of unresectable primary liver cancer to predict immunotherapy response |
| topic | efficacy prediction model immune‐checkpoint inhibition‐based therapy peripheral immune landscapes primary liver cancer |
| url | https://doi.org/10.1002/advs.202309631 |
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