Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation

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 samp...

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Published inNPJ precision oncology Vol. 5; no. 1; p. 27
Main Authors Yoon, Sang-Ho, Choi, Seo-Won, Nam, Suk Woo, Lee, Kyoung Bun, Nam, Jin-Wu
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 26.03.2021
Nature Publishing Group
Nature Portfolio
Subjects
631/67/1504/1610/4029
631/67/1857
631/67/327
Cancer Research
Clinical outcomes
Gene expression
Gene Therapy
Hepatitis
Human Genetics
Immunotherapy
Internal Medicine
Liver cancer
Liver transplants
Lymphocytes
Medicine
Medicine & Public Health
Metabolism
Oncology
Principal components analysis
Proteins
Targeted cancer therapy
Tumors
Viral infections
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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.
AbstractList 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.
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.
ArticleNumber 27
Author Yoon, Sang-Ho
Choi, Seo-Won
Nam, Jin-Wu
Lee, Kyoung Bun
Nam, Suk Woo
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Snippet Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and...
Abstract Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in...
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SubjectTerms 631/67/1504/1610/4029
631/67/1857
631/67/327
Cancer Research
Clinical outcomes
Gene expression
Gene Therapy
Hepatitis
Human Genetics
Immunotherapy
Internal Medicine
Liver cancer
Liver transplants
Lymphocytes
Medicine
Medicine & Public Health
Metabolism
Oncology
Principal components analysis
Proteins
Targeted cancer therapy
Tumors
Viral infections
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Title Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation
URI https://link.springer.com/article/10.1038/s41698-021-00167-2
https://www.ncbi.nlm.nih.gov/pubmed/33772139
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