Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation
Abstract Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-021-00167-2 |
| _version_ | 1797430211779756032 |
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| author | Sang-Ho Yoon Seo-Won Choi Suk Woo Nam Kyoung Bun Lee Jin-Wu Nam |
| author_facet | Sang-Ho Yoon Seo-Won Choi Suk Woo Nam Kyoung Bun Lee Jin-Wu Nam |
| author_sort | Sang-Ho Yoon |
| collection | DOAJ |
| description | Abstract Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant tumor samples from a Korean HCC cohort in which 38 patients underwent total hepatectomy, as well as for 15 normal and 47 adjacent nontumor samples. Using in silico deconvolution of expression mixtures, 22 immune cell fractions for each sample were inferred, and validated with immune cell counting by immunohistochemistry. Cell type-specific immune signatures dynamically shifted from premalignant stages to the late HCC stage. Total hepatectomy patients displayed elevated immune infiltration and prolonged disease-free survival compared to the partial hepatectomy patients. However, patients who exhibited an infiltration of regulatory T cells (Tregs) during the pretransplantation period displayed a high risk of tumor relapse with suppressed immune responses, and pretreatment was a potential driver of Treg infiltration in the total hepatectomy group. Treg infiltration appeared to be independent of molecular classifications based on transcriptomic data. Our study provides not only comprehensive immune signatures in adjacent nontumor lesions and early malignant HCC stages but also clinical guidance for HCC patients who will undergo liver transplantation. |
| first_indexed | 2024-03-09T09:25:20Z |
| format | Article |
| id | doaj.art-be2d57dbb8d94979ae11c1777d38e809 |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-09T09:25:20Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-be2d57dbb8d94979ae11c1777d38e8092023-12-02T06:20:54ZengNature Portfolionpj Precision Oncology2397-768X2021-03-015111310.1038/s41698-021-00167-2Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantationSang-Ho Yoon0Seo-Won Choi1Suk Woo Nam2Kyoung Bun Lee3Jin-Wu Nam4Department of Life Science, College of Natural Sciences, Hanyang UniversityDepartment of Life Science, College of Natural Sciences, Hanyang UniversityDepartment of Pathology, College of Medicine, The Catholic University of KoreaDepartment of Pathology, College of Medicine, Seoul National UniversityDepartment of Life Science, College of Natural Sciences, Hanyang UniversityAbstract Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant tumor samples from a Korean HCC cohort in which 38 patients underwent total hepatectomy, as well as for 15 normal and 47 adjacent nontumor samples. Using in silico deconvolution of expression mixtures, 22 immune cell fractions for each sample were inferred, and validated with immune cell counting by immunohistochemistry. Cell type-specific immune signatures dynamically shifted from premalignant stages to the late HCC stage. Total hepatectomy patients displayed elevated immune infiltration and prolonged disease-free survival compared to the partial hepatectomy patients. However, patients who exhibited an infiltration of regulatory T cells (Tregs) during the pretransplantation period displayed a high risk of tumor relapse with suppressed immune responses, and pretreatment was a potential driver of Treg infiltration in the total hepatectomy group. Treg infiltration appeared to be independent of molecular classifications based on transcriptomic data. Our study provides not only comprehensive immune signatures in adjacent nontumor lesions and early malignant HCC stages but also clinical guidance for HCC patients who will undergo liver transplantation.https://doi.org/10.1038/s41698-021-00167-2 |
| spellingShingle | Sang-Ho Yoon Seo-Won Choi Suk Woo Nam Kyoung Bun Lee Jin-Wu Nam Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation npj Precision Oncology |
| title | Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation |
| title_full | Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation |
| title_fullStr | Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation |
| title_full_unstemmed | Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation |
| title_short | Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation |
| title_sort | preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation |
| url | https://doi.org/10.1038/s41698-021-00167-2 |
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