Journal of Liver Cancer

Original Article

The effects of immune checkpoint modulators on the clinical course of patients with resectable hepatocellular carcinoma: Jihyun An, Hyo Jeong Kang, Eunsil Yu, Han Chu Lee, Ju Hyun Shim; J Liver Cancer. 2022;22(1):40-50. Published online March 17, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.06

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Background/Aim
Immune checkpoint proteins regulating T-cell mediated anti-tumor immunity have been reported to affect clinical outcomes in multiple malignancies. This study aimed to investigate the prognostic effect of histological expression of immune checkpoint proteins in patients with resected hepatocellular carcinoma (HCC).
Methods
A total of 221 patients with HCC who underwent curative resection were included. Expression of programmed-cell death ligand-1 (PD-L1) in tumor cells (tPD-L1) and tumor infiltrating mononuclear cells (TIMCs) (iPD-L1), programmed-cell death-1 in TIMCs (iPD-1), and cytotoxic T lymphocyte antigen-4 in TIMCs (iCTLA-4) were measured immunohistochemically.
Results
Histo-positivity for iCTLA-4, iPD-1, iPD-L1, and tPD-L1 was 32.1%, 42.5%, 35.3%, and 14.9%, respectively. Multivariate logistic analyses revealed that male sex and tumor >5 cm were variables related to iCTLA-4 positivity (odds ratio [OR], 0.46 and 1.94, respectively; P<0.05). Poor differentiation was related to PD-L1 expression in both tumor cells and TIMCs (OR, 2.88 and 3.46, respectively; P<0.05). Microvascular invasion was significantly associated only with iPD-L1 (OR, 2.24; P<0.05). In time-dependent outcome analyses, expression of immune checkpoint proteins in TIMCs (i.e., iCTLA-4, iPD-1, and iPD-L1) was significantly related to longer overall survival and non-cancer-related survival (all P<0.05), but not to time-to-recurrence or cancer-specific deaths. Concurrent activation of the PD-1:PD-L1 and CTLA-4 pathways predicted improved outcomes in terms of overall survival and non-cancer related survival (P=0.06 and P=0.03, respectively).
Conclusions
Immune checkpoint proteins upregulated in TIMCs in HCC tissues have individual and additive effects in prolonging the survival of patients, specifically in terms of survival not related to cancer recurrence.

Citations

Citations to this article as recorded by

The role of PD-1/PD-L1 signaling pathway in cancer pathogenesis and treatment: a systematic review
Amirhosein Sabaghian, Shahnam Shamsabadi, Saghar Momeni, Mobina Mohammadikia, Kiarash Mohebbipour, Samira Sanami, Sajjad Ahmad, Nahid Akhtar, Neeta Raj Sharma, Raja Babu Singh Kushwah, Yash Gupta, Ajit Prakash, Hamidreza Pazoki-Toroudi
Journal of Cancer Metastasis and Treatment.2024;[Epub] CrossRef
Recent Advances in Immune-based Therapy for Hepatocellular Carcinoma
Kyung Won Park, Tae Hoon Park, Eun Ji Jang, Pil Soo Sung
Journal of Digestive Cancer Research.2024; 12(2): 115. CrossRef

Review Article

Recent updates on the classification of hepatoblastoma according to the International Pediatric Liver Tumors Consensus: Se Un Jeong, Hyo Jeong Kang; J Liver Cancer. 2022;22(1):23-29. Published online March 17, 2022; DOI: https://doi.org/10.17998/jlc.2022.02.24

8,067 Views
594 Downloads
6 Citations

Abstract PDF

Hepatoblastoma is the most common pediatric liver malignancy and usually occurs within the first 3 years of life. In recent years, the overall incidence of hepatoblastoma has exhibited the greatest increase among all pediatric malignancies worldwide. The diagnosis of hepatoblastoma may be challenging due to the lack of a current consensus classification system. The International Pediatric Liver Tumors Consensus introduced guidelines and a consensus classification for the diagnosis of hepatoblastoma as either epithelial or mixed epithelial and mesenchymal and in the updated 5^th edition of the World Health Organization Classification of Digestive System Tumors.

Citations

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ACG Case Reports Journal.2024; 11(9): e01491. CrossRef
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