The general relevance of the immune system for cancer development and therapy is increasingly recognized. However and although the immune contexture of most human cancer types has been determined, a global characterisation of the immune tumour microenvironment in hepatocellular carcinoma (HCC) is lacking. Equally, differences in the immune contexture of HCC between different patient subgroups and its effect on survival remain to be established. Here we report an in silico analysis of the immune contexture of human HCC. Using large deep sequencing HCC tumour, adjacent non-tumour and healthy liver high-dimensional data sets, we were able to reveal previously unrecognized differences in the immune contexture of HCC. Strikingly, we found that different etiologies and HCC stages were not associated with major changes in the immune contexture. In contrast, the presence of T cells and cytotoxic cells as well as the absence of macrophages and Th2 cells positively correlated with patient survival. Based on these novel findings, we developed a prognostic score that accurately distinguishes between patients with good and poor survival. Our study provides the first global characterisation of the immune contexture of HCC and will have direct implications for future HCC therapies.
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http://dx.doi.org/10.1038/s41598-018-21937-2 | DOI Listing |
J Immunother Cancer
January 2025
NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
Background: The E3 ubiquitin ligase murine double minute 2 (MDM2) binds the p53 transcriptional activation domain and acts as a potent inhibitor of pathway, one of the three most crucial oncogenic pathways in urothelial carcinoma (UC). However, the clinical significance and impact on tumor immune contexture of amplification in UC remain unclear.
Methods: This study analyzed 240 patients with UC with matched clinical annotations from two local cohorts (ZSHS cohort and FUSCC cohort).
Methods Mol Biol
November 2024
Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 1138, Cordeliers Research Center, Laboratory "Cancer, Immune Control and Escape", Paris, France.
The tumor microenvironment is a complex network of interacting cells composed of immune and nonimmune cells. It has been reported that the composition of the immune contexture has a significant impact on tumor growth and patient survival in different solid tumors. For instance, we and other groups have previously demonstrated that a strong infiltration of T-helper type 1 (Th1), memory CD8 T cells, and immune cells organized into tertiary lymphoid structures is associated with the long-term survival of cancer patients.
View Article and Find Full Text PDFCancers (Basel)
November 2024
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Background: Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses.
Methods: Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro.
NPJ Precis Oncol
November 2024
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Local structures formed by cells in the tumor microenvironment (TME) play an important role in tumor development and treatment response. This study introduces SPoTLIghT, a computational framework providing a quantitative description of the tumor architecture from hematoxylin and eosin (H&E) slides. We trained a weakly supervised machine learning model on melanoma patients linking tile-level imaging features extracted from H&E slides to sample-level cell type quantifications derived from RNA-sequencing data.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
October 2024
Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA.
Chemokines bind to specific chemokine receptors, known as cell surface G protein-coupled receptors, constructing chemokine axes which lead to cell migration and invasion in developmental stage, pathophysiological process, and immune reactions. The chemokine axes in the tumor microenvironment are involved in tumor growth, angiogenesis, cancer stem-like cell properties, metastasis, and chemoresistance, modifying tumor immune contexture and cancer progression. Clinical features, including tumor state, grade, lymph node metastasis, and cancer subtypes, are related to the specific chemokine axes, which play a significant role in immune contexture and cell to cell interaction in the tumor microenvironment, followed by altered cancer prognosis and overall survival.
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