The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
PD‐1 and PD‐L1 upregulation promotes CD8+ T‐cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients
Abstract
Programmed death 1 (PD‐1) and its ligand (PD‐L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of cytotoxic CD8+ T lymphocytes, the main effector cells in hepatocellular carcinoma (HCC) patients, are not well defined. In this study, we characterized circulating and intratumor PD‐1/PD‐L1 expression and analyzed their association with disease progression in a cohort of hepatitis B virus‐infected patients, including 56 with HCC, 20 with liver cirrhosis (LC) and 20 healthy controls (HC). The frequency of circulating PD‐1+CD8+ T cells increased with disease progression from LC to HCC patients versus HC. Furthermore, tumor‐infiltrating effector CD8+ T cells showed a drastic increase in PD‐1 expression. These increases in circulating and intratumor PD‐1+CD8+ T cells could predict poorer disease progression and postoperative recurrence. Immunohistochemical staining showed that PD‐L1 expressing hepatoma cells and apoptotic infiltrating CD8+ T cells were both enriched in tumor sections. In vitro, CD8+ T cells induced PD‐L1 expression on hepatoma cells in an IFN‐γ–dependent manner, which in turn promoted CD8+ T cells apoptosis, and blocking PD‐L1 reversed this effect. Therefore, this study extends our knowledge of the role of the PD‐1/PD‐L1 pathway in tumor evasion and provides evidence for a new therapeutic target in HCC patients.
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Cited by
El-Khoueiry, A. B., Sangro, B., Yau, T., Crocenzi, T. S., Kudo, M., Hsu, C., Kim, T.-Y., Choo, S.-P., Trojan, J., Welling, T. H., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31046-2 · Cited by 4,280
Zhu, A. X., Finn, R. S., Edeline, J., Cattan, S., Ogasawara, S., Palmer, D., Verslype, C., Zagonel, V., Fartoux, L., Vogel, A., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30351-6 · Cited by 2,479
Genetic landscape and biomarkers of hepatocellular carcinoma
Zucman-Rossi, J., Villanueva, A., Nault, J.-C., & Llovet, J. M. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.061 · Cited by 1,325
Advances in immunotherapy for hepatocellular carcinoma
Sangro, B., Sarobe, P., Hervás-Stubbs, S., & Melero, I. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00438-0 · Cited by 1,306
PD-L1 expression in human cancers and its association with clinical outcomes
Yu, J., Wang, X., Teng, F., & Kong, L. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s105862 · Cited by 787
Metadata
- Authors
- Shi, F., Shi, M., Zeng, Z., Qi, R., Liu, Z., Zhang, J., Yang, Y., Tien, P., & Wang, F.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2010-12-22
- Volume
- 128
- Issue
- 4
- Pages
- 887-896
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2107564997
- Cited by
- 464
- References
- 11
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: PD‐1 and PD‐L1 upregulation promotes CD8+ T‐cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. https://app.cochat.ai/papers/10.1002/ijc.25397
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- Shi, F., Shi, M., Zeng, Z., Qi, R., Liu, Z., Zhang, J., Yang, Y., Tien, P., & Wang, F. (2011). PD‐1 and PD‐L1 upregulation promotes CD8+ T‐cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. International Journal of Cancer. https://doi.org/10.1002/ijc.25397
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