Liver sinusoidal endothelial cells regulate the balance between hepatic immunosuppression and immunosurveillance DOI Creative Commons
Kimberly N. Kremer,

Hadeel A. Khammash,

Anjelica M. Miranda

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 17, 2025

As a metabolic center, the liver prevents inappropriate immune responses to abundant dietary antigens within that could result in injury. This self-preservation mechanism can however decrease efficiency of immunosurveillance malignant cells by CD8 T cells. Hepatocellular carcinoma (HCC) is initiated chronic viral infections, alcohol consumption, and/or fatty diet leads injury, fibrosis, and cirrhosis. HCC patients have high levels dysfunctional exhausted cells, however, it unclear which stage development contributes cell dysfunction. Repair injury interactions between injured hepatocytes sinusoidal endothelial (LSEC), lead fibrosis. Here, using diethylnitrosamine/carbon tetrachloride (DEN/CCl4) mouse model early development, we demonstrate fibrosis are sufficient induce exhaustion signature with corresponding increase expression immunosuppressive molecules on LSEC. We show LSEC alter function at various stages differentiation/activation. compete dendritic presenting same antigen naïve resulting unique phenotype. Furthermore, abrogate killing target an antigen-dependent manner, previously activated effector change cytokine profile. Moreover, functional under low dose stimulation conditions. Thus, critically regulate balance preventing/limiting permitting tumor normal hepatic functions likely contributing conditions insult.

Language: Английский

T cell exhaustion and senescence for ovarian cancer immunotherapy DOI
Jiao Zhao,

Zhongmiao Wang,

Yingying Tian

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 104-105, P. 1 - 15

Published: July 18, 2024

Language: Английский

Citations

10
Targeting T cell exhaustion: emerging strategies in non-small cell lung cancer DOI Creative Commons
Xianqiang Liu, Xiaowei Xi, Shengshan Xu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 12, 2024

Lung cancer continues to be a major contributor cancer-related deaths globally. Recent advances in immunotherapy have introduced promising treatments targeting T cell functionality. Central the efficacy of these therapies is role cells, which are often rendered dysfunctional due continuous antigenic stimulation tumor microenvironment–a condition referred as exhaustion. This review addresses critical challenge exhaustion non-small lung (NSCLC), offering detailed examination its molecular underpinnings and resultant therapeutic ineffectiveness. We synthesize current knowledge on drivers exhaustion, evaluate emerging strategies for reversal, explore potential impact insights enhancing clinical immunotherapies. By consolidating reported trials preclinical studies, this article highlights innovative approaches modulate immune responses improve patient outcomes, thus providing roadmap future research development immunotherapy.

Language: Английский

Citations

8
Liver sinusoidal endothelial cells regulate the balance between hepatic immunosuppression and immunosurveillance DOI Creative Commons
Kimberly N. Kremer,

Hadeel A. Khammash,

Anjelica M. Miranda

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 17, 2025

As a metabolic center, the liver prevents inappropriate immune responses to abundant dietary antigens within that could result in injury. This self-preservation mechanism can however decrease efficiency of immunosurveillance malignant cells by CD8 T cells. Hepatocellular carcinoma (HCC) is initiated chronic viral infections, alcohol consumption, and/or fatty diet leads injury, fibrosis, and cirrhosis. HCC patients have high levels dysfunctional exhausted cells, however, it unclear which stage development contributes cell dysfunction. Repair injury interactions between injured hepatocytes sinusoidal endothelial (LSEC), lead fibrosis. Here, using diethylnitrosamine/carbon tetrachloride (DEN/CCl4) mouse model early development, we demonstrate fibrosis are sufficient induce exhaustion signature with corresponding increase expression immunosuppressive molecules on LSEC. We show LSEC alter function at various stages differentiation/activation. compete dendritic presenting same antigen naïve resulting unique phenotype. Furthermore, abrogate killing target an antigen-dependent manner, previously activated effector change cytokine profile. Moreover, functional under low dose stimulation conditions. Thus, critically regulate balance preventing/limiting permitting tumor normal hepatic functions likely contributing conditions insult.

Language: Английский

Citations

0