TIGIT Can Exert Immunosuppressive Effects on CD8+ T Cells by the CD155/TIGIT Signaling Pathway for Hepatocellular Carcinoma In Vitro

The efficacy of adoptive cellular immunotherapy against cancer cells is limited due to the presence of immunosuppressive cells within the solid tumor microenvironment. The upregulation of certain coinhibitory receptors may lead to exhaustion of the immune effector cells. T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an immune inhibitory receptor expressed by regulatory T cells and activated T cells and natural killer cells. The aim of this study was to determine the immunosuppressive effects of CD155/TIGIT signaling on CD8+ T cells of adoptive cellular immunotherapy in hepatocellular carcinoma (HCC). Our studies found that CD155 was overexpressed in HCC, and CD155hi HCC cells upregulated TIGIT on CD8+ T cells, which decreased the secretion of interferon-γ, tumor necrosis factor-α, and interleukin-17A and increased that of interleukin-10 from the effector cells. However, TIGIT blockade or CD155-knockdown reversed the inhibitory effect of HCC cells on CD8+ T-cell effector function. These results indicate that TIGIT can exert an immunosuppressive effect on CD8 T cells by modulating cytokine production through CD155, and is a promising target to optimize adoptive cellular immunotherapy against HCC.
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Basic Studies Source Type: research

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ConclusionThe riskScore obtained from an immune-related lncRNA signature could successfully predict the survival time and reflect the efficacy of immune checkpoint inhibitors. More importantly, it is possible to select different treatments for different hepatocellular carcinoma patients that increase the response rate of immune checkpoint inhibitors and will help improve the individualized treatment of hepatocellular carcinoma.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Adding the drug ramucirumab to gemcitabine chemotherapy worked especially well in a recent clinical trial involving second-line treatment for patients with pleural mesothelioma. Ramucirumab, an immunotherapy drug also known by the brand name Cyramza, is a monoclonal antibody that works by targeting and restricting a protein that stimulates blood vessel growth within tumors. Impressive results in the phase II clinical trial moved the drug combination closer to filling the long-standing void for a second-line mesothelioma treatment. The Lancet Oncology recently published results of the study, which was conducted in ...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
CONCLUSION: Herein, we reported the status of HRD using a cancer-panel for various solid tumor patients in routine clinical practice and demonstrated that HRD as a single biomarker was not sufficient to predict efficacy of ICIs in solid tumor patients.PMID:34510272 | DOI:10.1007/s00432-021-03781-6
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Source Type: research
ConclusionWe constructed a new ferroptosis-related mRNA/lncRNA signature for HCC patients. The model can be used for prognostic prediction and immune evaluation, providing a reference for immunotherapies and targeted therapies.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Channels (Austin). 2021 Dec;15(1):541-554. doi: 10.1080/19336950.2021.1968592.ABSTRACTHepatocellular carcinoma (HCC) is the most common subtype of liver cancer. Many patients with hepatocellular carcinoma are diagnosed at an advanced stage because the early symptoms are not obvious. For advanced hepatocellular carcinoma, immunotherapy and targeted therapy seem to be a promising direction. Finding a new prognostic marker for hepatocellular carcinoma and exploring its role in the immune microenvironment is of great value. ABCC transporters have previously been associated with drug resistance in hepatocellular tumors, but the...
Source: Channels - Category: Molecular Biology Authors: Source Type: research
ConclusionsFrom our data we conclude that the newly designed recombinant Ad5sPD1PVR virus significantly enhances CD8+ T cell-mediated antitumor efficacy with long-term tumor-specific immune surveillance in hepatocellular carcinoma, and that fludarabine is a promising therapeutic partner for Ad5sPD1PVR.
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research
Liver Cancer
Source: Liver Cancer - Category: Cancer & Oncology Source Type: research
Hepatocellular cancer is the sixth most frequently diagnosed malignant disease worldwide, and was responsible for tens of millions of deaths in 2020; however, treatment options for patients with advanced hepatocellular carcinoma remain limited. Immunotherapy has undergone rapid development over recent years, especially in the field of immune checkpoint inhibitors (ICIs). These drugs aim to activate and enhance antitumor immunity and represent a new prospect for the treatment of patients with advanced cancer. Nevertheless, only a small proportion of liver cancer patients currently benefit from ICI-based treatment, highlight...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Hepatocellular carcinoma (HCC) is an aggressive cancer with a high rate of death globally. The use of bioinformatics may help to identify immune cell-related genes both as targets for potential immunotherapies...
Source: Cancer Cell International - Category: Cancer & Oncology Authors: Tags: Primary research Source Type: research
We examined the effects of a DGKα inhibitor (DGKAI) on liver cancer cell proliferation and cytokine production by immune cells in vitro and on tumorigenesis and host immunity in a hepatocellular carcinoma (HCC) mouse model. Oral DGKAI significantly suppressed tumor growth and prolonged survival in model mice. Tumor infiltration of T cells and dendritic cells was also enhanced in mice treated with DGKAI, and the production of cytokines and cytotoxic molecules by CD4+ and CD8+ T cells was increased. Depletion of CD8+ T cells reduced the effect of DGKAI. Furthermore, interferon- γ stimulation augmented the express...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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