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Prognostic and therapeutic potential of imbalance between PD-1+CD8 and ICOS+Treg cells in advanced HBV-HCC.
- Source :
-
Cancer science [Cancer Sci] 2024 Aug; Vol. 115 (8), pp. 2553-2564. Date of Electronic Publication: 2024 Jun 15. - Publication Year :
- 2024
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Abstract
- Over 50% of patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) are diagnosed at an advanced stage, which is characterized by immune imbalance between CD8+ T cells and regulatory T (Treg) cells that accelerates disease progression. However, there is no imbalance indicator to predict clinical outcomes. Here, we show that the proportion of CD8+ T cells decreases and Treg cells increases in advanced HBV-HCC patients. During this stage, CD8+ T cells and Treg cells expressed the coinhibitory molecule PD-1 and the costimulatory molecule ICOS, respectively. Additionally, the ratio between PD-1+CD8 and ICOS+Tregs showed significant changes. Patients were further divided into high- and low-ratio groups: PD-1+CD8 and ICOS+Tregs high- (PD-1/ICOS <superscript>hi</superscript> ) and low-ratio (PD-1/ICOS <superscript>lo</superscript> ) groups according to ratio median. Compared with PD-1/ICOS <superscript>lo</superscript> patients, the PD-1/ICOS <superscript>hi</superscript> group had better clinical prognosis and weaker CD8+ T cells exhaustion, and the T cell-killing and proliferation functions were more conservative. Surprisingly, the small sample analysis found that PD-1/ICOS <superscript>hi</superscript> patients exhibited a higher proportion of tissue-resident memory T (T <subscript>RM</subscript> ) cells and had more stable killing capacity and lower apoptosis capacity than PD-1/ICOS <superscript>lo</superscript> advanced HBV-HCC patients treated with immune checkpoint inhibitors (ICIs). In conclusion, the ratio between PD-1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced HBV-HCC. These findings provide significant clinical implications for the prognosis of advanced HBV-HCC and may serve as a theoretical basis for identifying new targets in immunotherapy.<br /> (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Humans
Prognosis
Male
Female
Middle Aged
Hepatitis B virus immunology
Immune Checkpoint Inhibitors therapeutic use
Immune Checkpoint Inhibitors pharmacology
Adult
Aged
Hepatitis B immunology
Programmed Cell Death 1 Receptor metabolism
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Inducible T-Cell Co-Stimulator Protein metabolism
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Liver Neoplasms immunology
Liver Neoplasms pathology
Liver Neoplasms virology
Liver Neoplasms metabolism
Carcinoma, Hepatocellular immunology
Carcinoma, Hepatocellular pathology
Carcinoma, Hepatocellular virology
Carcinoma, Hepatocellular metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 115
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 38877825
- Full Text :
- https://doi.org/10.1111/cas.16247