State of CD8+ T cells in progression from nonalcoholic steatohepatitis to hepatocellular carcinoma: From pathogenesis to immunotherapy
With the obesity epidemic, nonalcoholic steatohepatitis (NASH) is emerging as the fastest growing potential cause of hepatocellular carcinoma (HCC). NASH has been demonstrated to establish a tumor-prone liver microenvironment where both innate and adaptive immune systems are involved. As the most ty...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223009228 |
| _version_ | 1797744075456118784 |
|---|---|
| author | Xin Zhong Minling Lv MengQing Ma Qi Huang Rui Hu Jing Li Jinyu Yi Jialing Sun Xiaozhou Zhou |
| author_facet | Xin Zhong Minling Lv MengQing Ma Qi Huang Rui Hu Jing Li Jinyu Yi Jialing Sun Xiaozhou Zhou |
| author_sort | Xin Zhong |
| collection | DOAJ |
| description | With the obesity epidemic, nonalcoholic steatohepatitis (NASH) is emerging as the fastest growing potential cause of hepatocellular carcinoma (HCC). NASH has been demonstrated to establish a tumor-prone liver microenvironment where both innate and adaptive immune systems are involved. As the most typical anti-tumor effector, the cell function of CD8+ T cells is remodeled by chronic inflammation, metabolic alteration, lipid toxicity and oxidative stress in the liver microenvironment along the NASH to HCC transition. Unexpectedly, NASH may blunt the effect of immune checkpoint inhibitor therapy against HCC due to the dysregulated CD8+ T cells. Growing evidence has supported that NASH is likely to facilitate the state transition of CD8+ T cells with changes in cell motility, effector function, metabolic reprogramming and gene transcription according to single-cell sequencing. However, the mechanistic insight of CD8+ T cell states in the NASH-driven HCC is not comprehensive. Herein, we focus on the characterization of state phenotypes of CD8+ T cells with both functional and metabolic signatures in NASH-driven fibrosis and HCC. The NASH-specific CD8+ T cells are speculated to mainly have a dualist effect, where its aberrant activated phenotype sustains chronic inflammation in NASH but subsequently triggers its exhaustion in HCC. As the exploration of CD8+ T cells on the distribution and phenotypic shifts will provide a new direction for the intervention strategies against HCC, we also discuss the implications for targeting different phenotypes of CD8+ T cells, shedding light on the personalized immunotherapy for NASH-driven HCC. |
| first_indexed | 2024-03-12T15:05:31Z |
| format | Article |
| id | doaj.art-9242241005334baead45bb60c112f31b |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-12T15:05:31Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-9242241005334baead45bb60c112f31b2023-08-13T04:52:42ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115131State of CD8+ T cells in progression from nonalcoholic steatohepatitis to hepatocellular carcinoma: From pathogenesis to immunotherapyXin Zhong0Minling Lv1MengQing Ma2Qi Huang3Rui Hu4Jing Li5Jinyu Yi6Jialing Sun7Xiaozhou Zhou8Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China; Department of Liver Disease, the fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaDepartment of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China; Department of Liver Disease, the fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaDepartment of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China; Department of Liver Disease, the fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaDepartment of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China; Department of Liver Disease, the fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaDepartment of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China; Department of Liver Disease, the fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaDepartment of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China; Department of Liver Disease, the fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaDepartment of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China; Department of Liver Disease, the fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaDepartment of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China; Department of Liver Disease, the fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaDepartment of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China; Department of Liver Disease, the fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China; Correspondence to: Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Futian District, Shenzhen, Guangdong Province, China.With the obesity epidemic, nonalcoholic steatohepatitis (NASH) is emerging as the fastest growing potential cause of hepatocellular carcinoma (HCC). NASH has been demonstrated to establish a tumor-prone liver microenvironment where both innate and adaptive immune systems are involved. As the most typical anti-tumor effector, the cell function of CD8+ T cells is remodeled by chronic inflammation, metabolic alteration, lipid toxicity and oxidative stress in the liver microenvironment along the NASH to HCC transition. Unexpectedly, NASH may blunt the effect of immune checkpoint inhibitor therapy against HCC due to the dysregulated CD8+ T cells. Growing evidence has supported that NASH is likely to facilitate the state transition of CD8+ T cells with changes in cell motility, effector function, metabolic reprogramming and gene transcription according to single-cell sequencing. However, the mechanistic insight of CD8+ T cell states in the NASH-driven HCC is not comprehensive. Herein, we focus on the characterization of state phenotypes of CD8+ T cells with both functional and metabolic signatures in NASH-driven fibrosis and HCC. The NASH-specific CD8+ T cells are speculated to mainly have a dualist effect, where its aberrant activated phenotype sustains chronic inflammation in NASH but subsequently triggers its exhaustion in HCC. As the exploration of CD8+ T cells on the distribution and phenotypic shifts will provide a new direction for the intervention strategies against HCC, we also discuss the implications for targeting different phenotypes of CD8+ T cells, shedding light on the personalized immunotherapy for NASH-driven HCC.http://www.sciencedirect.com/science/article/pii/S0753332223009228Nonalcoholic steatohepatitisHepatocellular carcinomaCD8+ T cellInflammationMetabolismImmune checkpoint inhibitor |
| spellingShingle | Xin Zhong Minling Lv MengQing Ma Qi Huang Rui Hu Jing Li Jinyu Yi Jialing Sun Xiaozhou Zhou State of CD8+ T cells in progression from nonalcoholic steatohepatitis to hepatocellular carcinoma: From pathogenesis to immunotherapy Biomedicine & Pharmacotherapy Nonalcoholic steatohepatitis Hepatocellular carcinoma CD8+ T cell Inflammation Metabolism Immune checkpoint inhibitor |
| title | State of CD8+ T cells in progression from nonalcoholic steatohepatitis to hepatocellular carcinoma: From pathogenesis to immunotherapy |
| title_full | State of CD8+ T cells in progression from nonalcoholic steatohepatitis to hepatocellular carcinoma: From pathogenesis to immunotherapy |
| title_fullStr | State of CD8+ T cells in progression from nonalcoholic steatohepatitis to hepatocellular carcinoma: From pathogenesis to immunotherapy |
| title_full_unstemmed | State of CD8+ T cells in progression from nonalcoholic steatohepatitis to hepatocellular carcinoma: From pathogenesis to immunotherapy |
| title_short | State of CD8+ T cells in progression from nonalcoholic steatohepatitis to hepatocellular carcinoma: From pathogenesis to immunotherapy |
| title_sort | state of cd8 t cells in progression from nonalcoholic steatohepatitis to hepatocellular carcinoma from pathogenesis to immunotherapy |
| topic | Nonalcoholic steatohepatitis Hepatocellular carcinoma CD8+ T cell Inflammation Metabolism Immune checkpoint inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223009228 |
| work_keys_str_mv | AT xinzhong stateofcd8tcellsinprogressionfromnonalcoholicsteatohepatitistohepatocellularcarcinomafrompathogenesistoimmunotherapy AT minlinglv stateofcd8tcellsinprogressionfromnonalcoholicsteatohepatitistohepatocellularcarcinomafrompathogenesistoimmunotherapy AT mengqingma stateofcd8tcellsinprogressionfromnonalcoholicsteatohepatitistohepatocellularcarcinomafrompathogenesistoimmunotherapy AT qihuang stateofcd8tcellsinprogressionfromnonalcoholicsteatohepatitistohepatocellularcarcinomafrompathogenesistoimmunotherapy AT ruihu stateofcd8tcellsinprogressionfromnonalcoholicsteatohepatitistohepatocellularcarcinomafrompathogenesistoimmunotherapy AT jingli stateofcd8tcellsinprogressionfromnonalcoholicsteatohepatitistohepatocellularcarcinomafrompathogenesistoimmunotherapy AT jinyuyi stateofcd8tcellsinprogressionfromnonalcoholicsteatohepatitistohepatocellularcarcinomafrompathogenesistoimmunotherapy AT jialingsun stateofcd8tcellsinprogressionfromnonalcoholicsteatohepatitistohepatocellularcarcinomafrompathogenesistoimmunotherapy AT xiaozhouzhou stateofcd8tcellsinprogressionfromnonalcoholicsteatohepatitistohepatocellularcarcinomafrompathogenesistoimmunotherapy |