Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation
Abstract Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as the most promising strategy for hepatocellular carcinoma (HCC) downstaging prior to liver transplantation (LT). However, further evidence is required to assess the feasibility and safety of pretransplant ICI exposure. We r...
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| Format: | Article |
| Language: | English |
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Springer
2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03853-9 |
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| author | Xinjun Lu Qi Zhu Junfeng Cai Zuozhong Yang Guangxiang Gu Li Pang Mingye Su Fapeng Zhang Haoming Lin Wenrui Wu Leibo Xu Chao Liu |
| author_facet | Xinjun Lu Qi Zhu Junfeng Cai Zuozhong Yang Guangxiang Gu Li Pang Mingye Su Fapeng Zhang Haoming Lin Wenrui Wu Leibo Xu Chao Liu |
| author_sort | Xinjun Lu |
| collection | DOAJ |
| description | Abstract Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as the most promising strategy for hepatocellular carcinoma (HCC) downstaging prior to liver transplantation (LT). However, further evidence is required to assess the feasibility and safety of pretransplant ICI exposure. We retrospective analyzed 159 HCC patients who underwent LT at our institution from June 2019 to December 2023, and 39 recipients (39/159, 24.5%) received pretransplant ICI therapy. The perioperative acute rejection rate and rejection-related mortality rate in the ICI group were 23.1% (9/39) and 12.8% (5/39), respectively, which were significantly higher than those in the non-ICI group, at 5% (6/120, P = 0.002) and 0% (0/120, P = 0.001). There was no significant difference in the 90-day post-transplant overall survival (OS) (P = 0.447) and recurrence-free survival (RFS) (P = 0.723) between these two groups. We found 37.1% (59/159) recipients were found to have microvascular invasion (MVI), no matter whether the HCC tumor is within Milan criteria or not. Notably, though MVI was identified as a risk factor for the LT recipients, pretransplant ICI exposure appeared to be a protective factor for HCC patients with MVI which benefits its overall survival. Besides, the RFS and OS in the ICI exposure recipients with MVI were comparable to the non-ICI exposure recipients without MVI. However, no synergistic anti-tumor effects were observed with pretransplant ICI immunotherapy when combined with locoregional of TACE, HAIC, RFA and systematic of lenvatinib or sorafenib downstaging treatments, nor with post-transplant adjuvant of systematic or FOLFOX chemotherapy. Further comprehensive studies are needed to balance the dual natural effects of immunotherapy by optimizing downstaging protocols and patient selection to reduce acute rejection and improve long-term survival. |
| format | Article |
| id | doaj-art-402758c13d454e79bd28c29684e81ce8 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-402758c13d454e79bd28c29684e81ce82025-02-02T12:26:47ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-0174111110.1007/s00262-024-03853-9Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantationXinjun Lu0Qi Zhu1Junfeng Cai2Zuozhong Yang3Guangxiang Gu4Li Pang5Mingye Su6Fapeng Zhang7Haoming Lin8Wenrui Wu9Leibo Xu10Chao Liu11Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatobiliary Surgery, Sun Yat-Sen University Cancer CenterDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityAbstract Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as the most promising strategy for hepatocellular carcinoma (HCC) downstaging prior to liver transplantation (LT). However, further evidence is required to assess the feasibility and safety of pretransplant ICI exposure. We retrospective analyzed 159 HCC patients who underwent LT at our institution from June 2019 to December 2023, and 39 recipients (39/159, 24.5%) received pretransplant ICI therapy. The perioperative acute rejection rate and rejection-related mortality rate in the ICI group were 23.1% (9/39) and 12.8% (5/39), respectively, which were significantly higher than those in the non-ICI group, at 5% (6/120, P = 0.002) and 0% (0/120, P = 0.001). There was no significant difference in the 90-day post-transplant overall survival (OS) (P = 0.447) and recurrence-free survival (RFS) (P = 0.723) between these two groups. We found 37.1% (59/159) recipients were found to have microvascular invasion (MVI), no matter whether the HCC tumor is within Milan criteria or not. Notably, though MVI was identified as a risk factor for the LT recipients, pretransplant ICI exposure appeared to be a protective factor for HCC patients with MVI which benefits its overall survival. Besides, the RFS and OS in the ICI exposure recipients with MVI were comparable to the non-ICI exposure recipients without MVI. However, no synergistic anti-tumor effects were observed with pretransplant ICI immunotherapy when combined with locoregional of TACE, HAIC, RFA and systematic of lenvatinib or sorafenib downstaging treatments, nor with post-transplant adjuvant of systematic or FOLFOX chemotherapy. Further comprehensive studies are needed to balance the dual natural effects of immunotherapy by optimizing downstaging protocols and patient selection to reduce acute rejection and improve long-term survival.https://doi.org/10.1007/s00262-024-03853-9HCCLiver transplantationImmune checkpoint inhibitorAcute rejectionMVI |
| spellingShingle | Xinjun Lu Qi Zhu Junfeng Cai Zuozhong Yang Guangxiang Gu Li Pang Mingye Su Fapeng Zhang Haoming Lin Wenrui Wu Leibo Xu Chao Liu Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation Cancer Immunology, Immunotherapy HCC Liver transplantation Immune checkpoint inhibitor Acute rejection MVI |
| title | Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation |
| title_full | Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation |
| title_fullStr | Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation |
| title_full_unstemmed | Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation |
| title_short | Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation |
| title_sort | pretransplant immunotherapy increases acute rejection yet improves survival outcome of hcc patients with mvi post liver transplantation |
| topic | HCC Liver transplantation Immune checkpoint inhibitor Acute rejection MVI |
| url | https://doi.org/10.1007/s00262-024-03853-9 |
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