Cross-talk between TNF- α and IFN-γ signaling in induction of B7-H1 expression in hepatocellular carcinoma cells

AbstractClinical benefit from immunotherapy of B7-H1/PD-1 checkpoint blockade indicates that it is important to understand the regulatory mechanism of B7-H1 expression in cancer cells. As an adaptive response to the endogenous antitumor immunity, B7-H1 expression is up-regulated in HCC cells. B7-H1 expression is induced mainly by IFN- γ released from tumor-infiltrating T cells in HCC. In addition, HCC is a prototype of inflammation-related cancer and TNF-α is a critical component of inflammatory microenvironment of HCC. In the present study, we asked whether TNF-α can promote the expression of B7-H1 induced by IFN-γ in HCC ce lls. We found that JAK/STAT1/IRF1 was the primary pathway responsible for induction of B7-H1 expression by IFN-γ in human HCC cell lines. TNF-α and IFN-γ synergistically induced the expression of B7-H1 in the HCC cells. Moreover, the mechanism of the synergy was that TNF-α enhanced IFN-γ signal ing by upregulating the expression of IFN-γ receptors. Furthermore, B7-H1 expression induced synergistically by TNF-α and IFN-γ in murine HCC cells facilitated tumor growth in vivo. Our findings suggest that TNF-α may enhance the adaptive immune resistance mediated by IFN-γ-induced B7-H1 in HCC cells.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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iang Ou Liver cancer is one of the dominant causes of cancer-related mortality, and the survival rate of liver cancer is among the lowest for all cancers. Immunotherapy for hepatocellular carcinoma (HCC) has yielded some encouraging results, but the percentage of patients responding to single-agent therapies remains low. Therefore, potential directions for improved immunotherapies include identifying new immune targets and checkpoints and customizing treatment procedures for individual patients. The development of combination therapies for HCC is also crucial and urgent and, thus, further studies are required. Mice hav...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ConclusionsThe epigenetic modificator EZH2 can suppress the expression of immune checkpoint inhibitor PD-L1 by directly upregulating the promoter H3K27me3 levels ofCD274 andIRF1 in hepatoma cells, and might serve as a potential therapeutic target for combination of immunotherapy for immune-activated HCC.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
AbstractImmune checkpoint inhibition suggests promising progress for the treatment of advanced hepatocellular carcinoma (HCC). However, the underlying cellular mechanisms remain unclear because liver cancer cells apparently do not upregulate inhibitory checkpoint molecules. Here, we analysed whether regulatory T cells (Tregs) can alternatively trigger checkpoint inhibition pathways in HCC. Using flow cytometry we analysed expression of checkpoint molecules (PD-1, PD-L1, CTLA-4, GITR, Tim-3) on peripheral CD4+CD25+Foxp3+ Tregs and their secretion of inhibitory mediators (IL-10, IL-35, TGF-beta, galectin-9) in 116 individual...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Yicheng Ni Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with localized diseas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
In conclusion, PD-1+ TIGIT+ CD8+ T-cell populations are associated with accelerated disease progression and poor outcomes in HBV-HCC, which might not only have important clinical implications for prognosis but also provide a rationale for new targets in immunotherapy.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Abstract The combined immunotherapy of nivolumab and ipilimumab causes a variety of autoimmune-related adverse events (irAEs). The current report details a 70-year-old woman with clear cell renal cell carcinoma metastasis in the lung. Two weeks after two courses of treatment, the patient complained of headache, dizziness and nausea. Cerebrospinal fluid (CSF) analysis revealed an elevated protein level of 195 mg/dl and a significantly elevated white blood cell (WBC) count of 830/mm3 (lymphocytes, 825/mm3; neutrophils, 5/mm3). The results excluded malignancy and infection. The patient was diagnosed with aseptic meni...
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: Mol Clin Oncol Source Type: research
Publication date: Available online 5 November 2019Source: European UrologyAuthor(s): Alfonso Gómez de Liaño Lista, Nick van Dijk, Guillermo de Velasco Oria de Rueda, Andrea Necchi, Pernelle Lavaud, Rafael Morales-Barrera, Teresa Alonso Gordoa, Pablo Maroto, Alain Ravaud, Ignacio Durán, Bernadett Szabados, Daniel Castellano, Patrizia Giannatempo, Yohann Loriot, Joan Carles, Georgia Anguera Palacios, Felix Lefort, Daniele Raggi, Marine Gross Goupil, Thomas PowlesAbstractBackgroundImmune checkpoint inhibitors (ICIs) are approved for first-line (cisplatin unfit, PD-L1+) and platinum-refractory urothelial c...
Source: European Urology - Category: Urology & Nephrology Source Type: research
Publication date: Available online 1 November 2019Source: Biochimica et Biophysica Acta (BBA) - Reviews on CancerAuthor(s): David Anwanwan, Santosh Kumar Singh, Shriti Singh, Varma Saikam, Rajesh SinghAbstractGlobally, liver cancer is the most frequent fatal malignancy; in the United States, it ranks fifth. Patients are often diagnosed with liver cancer in advanced stages, contributing to its poor prognosis. Of all liver cancer cases,>90% are hepatocellular carcinomas (HCCs) for which chemotherapy and immunotherapy are the best options for therapy. For liver cancer patients, new treatment options are necessary. Use of n...
Source: Biochimica et Biophysica Acta (BBA) Reviews on Cancer - Category: Cancer & Oncology Source Type: research
Introduction: The prognosis for recurrent intrahepatic cholangiocarcinoma with bone metastasis remains dismal and its treatment poses a challenge for oncologists. To date, only 2 cases were reported in which pembrolizumab, an agent against programmed cell death protein-1 (PD-1), combined with chemotherapy led to a complete response.[1] The safety and efficacy of nivolumab-based immunotherapy combined with lenvatinibin intrahepatic cholangiocarcinoma is unknown. Patient concerns: A 40-year-old female was identified as having a lesion of 7.0 cm in diameter in the right lobe of the liver. In addition, calculi in the ma...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Conditions:   Hepatocellular Carcinoma;   Liver Cancer;   Cholangiocarcinoma Intervention:   Sponsor:   National Cancer Institute (NCI) Not yet recruiting
Source: - Category: Research Source Type: clinical trials
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