Publications by authors named "Firouzeh Korangy"
Functional tumor-specific CD8+ T cells are essential for an effective anti-tumor immune response and the efficacy of immune checkpoint inhibitor therapy. In comparison to other organ sites, we found higher numbers of tumor-specific CD8+ T cells in primary, metastatic liver tumors in murine tumor models. Despite their abundance, CD8+ T cells in the liver displayed an exhausted phenotype.
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- Liver cancer is one of the most lethal cancers, and this study explores the role of the vagus nerve in tumor progression by regulating immune responses through acetylcholine (ACh).
- Liver denervation showed a significant reduction in liver tumors, while increasing parasympathetic activity led to tumor growth, indicating a complex relationship between cholinergic signals and adaptive immunity.
- The findings reveal that gut bacteria can affect both behavior and liver anti-tumor immunity through interactions with the vagus nerve, suggesting potential for new treatment targets.
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- Liver metastases often resist immune checkpoint inhibitor (ICI) therapy, and regulatory T cells (Tregs) in the liver may contribute to this resistance, but their specific role is not well understood.* -
- The study utilized flow cytometry and RNA sequencing to analyze the behavior of hepatic Tregs, revealing a unique population that grows significantly in response to ICI treatment, regardless of tumor presence.* -
- The findings suggest that a specific subpopulation of CD29 Tregs in the liver is crucial for the enhanced suppression and resistance to ICI therapy, indicating their potential as targets for improving treatment outcomes.*
Immune-checkpoint inhibitors (ICIs) are now widely used for the treatment of patients with advanced-stage hepatocellular carcinoma (HCC). Two different ICI-containing regimens, atezolizumab plus bevacizumab and tremelimumab plus durvalumab, are now approved standard-of-care first-line therapies in this setting. However, and despite substantial improvements in survival outcomes relative to sorafenib, most patients with advanced-stage HCC do not derive durable benefit from these regimens.
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- * Fecal transplantation shows that this iNKT regulation is linked to microbiome changes rather than simply increasing the number of iNKT cells; it indicates an indirect effect since in vitro activated iNKT cells from vancomycin-treated mice do not exhibit increased activation.
- * The findings reveal that IL-18 from liver macrophages, particularly those expressing CSF-1R, is crucial for the enhanced iNKT activation, highlighting the gut microbiome's role in regulating immune response through these macrophages.
Mucosal-associated invariant T (MAIT) cells represent an abundant innate-like T cell subtype in the human liver. MAIT cells are assigned crucial roles in regulating immunity and inflammation, yet their role in liver cancer remains elusive. Here, we present a MAIT cell-centered profiling of hepatocellular carcinoma (HCC) using scRNA-seq, flow cytometry, and co-detection by indexing (CODEX) imaging of paired patient samples.
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- Immunotherapies for cancer are effective for some patients, but not all, highlighting the need to understand the immune environment of tumors better.
- Innate lymphoid cells (ILCs) and innate-like T cells (ILTCs) are crucial players in cancer's immune response, acting quickly to help bridge existing immunity.
- The review discusses the characteristics of ILCs and ILTCs, their impact on antitumor activity, and potential strategies for targeting them in future cancer treatments.
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- Platelets, often seen as just clotting agents, actually play a surprising role in promoting tumor growth and can also inhibit liver cancer (HCC) in mice with non-alcoholic fatty liver disease (NAFLD).
- The study showed that the anti-tumor effects of platelets come from their release of CD40L through a pathway involving the P2Y12 receptor, which helps activate CD8 T cells.
- Unlike traditional anti-platelet medications like aspirin, which don't affect CD40L release, this research suggests that targeting platelets without blocking CD40L could benefit liver cancer patients with NAFLD.
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- Innate lymphoid cells (ILCs) are diverse immune cells whose roles in liver cancer (specifically hepatocellular carcinoma or HCC) are still being discovered, including their presence in blood samples from HCC patients.
- A study analyzed ILCs in the peripheral blood of HCC patients before and after treatment with immune checkpoint inhibitors (ICIs), finding increased ILC1 and decreased ILC3 cells, as well as a unique subset of NK-like ILCs with cytotoxic markers that improved after treatment.
- The research revealed that changes in ILC populations, especially the NK-like ILCs, were linked to better patient outcomes, suggesting that ILCs could serve as valuable indicators for studying the innate immune
Innate lymphoid cells (ILCs) are a heterogenous population of the innate immune system, enriched at mucosal surfaces and are pivotal regulators of immune homeostasis. ILCs are the innate counterpart of T cells. Like T cells, ILC subsets are highly plastic with their composition and function controlled by alterations in their microenvironment.
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- The study investigates how the local environment of cytokines influences innate lymphoid cells (ILCs) in hepatocellular carcinoma (HCC), a cancer linked to inflammation.
- RNA sequencing and various cellular analyses from HCC samples revealed that cytokine gradients affect ILC types, with changes leading to altered immune functions that may relate to patient survival.
- High levels of ILC2 compared to ILC1, associated with the presence of interleukin-33, were linked to better survival outcomes, highlighting the tumor's cytokine environment as a critical factor in HCC prognosis.
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- Gut dysbiosis in patients with cirrhosis and chronic gastrointestinal disorders can negatively impact antitumor immunity in the liver, particularly in cases of cholangiocarcinoma.
- The study found that conditions like primary sclerosing cholangitis (PSC) and colitis lead to an increase in specific immune cells (PMN-MDSCs) that suppress the body's ability to fight tumors.
- Neomycin treatment was shown to counteract this immune suppression by blocking the expression of factors that promote these suppressive immune cells, suggesting a potential therapeutic avenue for liver cancer prevention.
Locoregional therapies are commonly used to treat patients with hepatocellular carcinoma. It has been noted for many years that locoregional therapies may have additional systemic effects other than simple tumour elimination. Immunological "side effects" have been described in response to locoregional therapies in animal studies and in patients.
View Article and Find Full Text PDFBackground: Checkpoint inhibitors have recently been approved for the treatment of patients with hepatocellular carcinoma (HCC). However, biomarkers, which will help identify patients responding to therapy, are missing. We recently tested the combination of anti-CTLA4 treatment (tremelimumab) with loco-regional therapy in patients with HCC and reported a partial response rate of 26%.
View Article and Find Full Text PDFTreatment options for patients with advanced biliary tract cancer are limited. Dysregulation of the immune system plays an important role in the pathogenesis of biliary tract cancer (BTC). This study aimed to investigate whether tremelimumab, an anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, could be combined safely with microwave ablation to enhance the effect of anti-CTLA4 treatment in patients with advanced BTC.
View Article and Find Full Text PDFBackground & Aims: Cytokine-induced killer (CIK) cell-based immunotherapy is effective as an adjuvant therapy in early stage hepatocellular carcinoma (HCC) but lacks efficacy in advanced HCC. We aimed to investigate immune suppressor mechanisms in HCC, focusing on the role of myeloid-derived suppressor cells (MDSCs) in response to CIK therapy.
Methods: MDSCs were quantified by flow cytometry and quantitative real-time PCR.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Immune checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies has shown promising results in the treatment of patients with advanced HCC. The anti-PD-1 antibody, nivolumab, is now approved for patients who have had progressive disease on the current standard of care.
View Article and Find Full Text PDFPrimary liver tumors and liver metastasis currently represent the leading cause of cancer-related death. Commensal bacteria are important regulators of antitumor immunity, and although the liver is exposed to gut bacteria, their role in antitumor surveillance of liver tumors is poorly understood. We found that altering commensal gut bacteria in mice induced a liver-selective antitumor effect, with an increase of hepatic CXCR6 natural killer T (NKT) cells and heightened interferon-γ production upon antigen stimulation.
View Article and Find Full Text PDFThe cross-talk between tumor cells, myeloid cells, and T cells can play a critical role in tumor pathogenesis and response to immunotherapies. Although the etiology of mesothelioma is well understood, the impact of mesothelioma tumor cells on the surrounding immune microenvironment is less well studied. In this study, the effect of the mesothelioma tumor microenvironment on circulating and infiltrating granulocytes and T cells is investigated.
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- * Identifying predictive and prognostic biomarkers is vital for progressing these therapies, prompting systematic approaches for monitoring immune responses.
- * The Immune Biomarkers Task Force, including experts from various fields, aims to provide guidelines on sample collection and analysis methods for assessing immune regulation and modulation in cancer treatment.
Background & Aims: Tremelimumab is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of activated T lymphocytes. Ablative therapies induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced hepatocellular carcinoma (HCC). This study aimed to demonstrate whether tremelimumab could be combined safely and feasibly with ablation.
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