WNT/β-Catenin Signaling Pathway Regulating T Cell-Inflammation in the Tumor Microenvironment

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Sept. 26, 2019

Immunotherapy with checkpoint inhibitors has greatly prolonged the overall survival of cancer patients in melanoma and many other types. However, only a subset shows clinical responses from these interventions, which was predicated by T cell-inflamed tumor microenvironment. phenotype is characterized infiltration CD8+ cells, CD8α/CD103-lineage dendritic cells (DCs), as well high density FoxP3+ Regulatory (Tregs) that are associated efficacy immune blockade. A number regulators been cell-inflammation microenvironment, WNT/β-catenin signaling one best characterized. The tumor-intrinsic activation frequently poor spontaneous cell across most human cancers. In this article, we will review essential roles non-T including development function exclusion immunosurveillance. We also discuss impact pathway driving microenvironment To improve immunotherapy efficacy, argue targeting Wnt/β-catenin should be priority for combinational therapy to restore infiltration.

Language: Английский

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Biomarkers for Predicting Response to Immunotherapy with Immune Checkpoint Inhibitors in Cancer Patients

Clinical Chemistry, Journal Year: 2019, Volume and Issue: 65(10), P. 1228 - 1238

Published: July 17, 2019

Abstract BACKGROUND Immunotherapy, especially the use of immune checkpoint inhibitors, has revolutionized management several different cancer types in recent years. However, for most cancer, only a minority patients experience durable response. Furthermore, administration immunotherapy can result serious adverse reactions. Thus, efficient and effective immunotherapy, accurate predictive biomarkers that have undergone analytical clinical validation are necessary. CONTENT Among widely investigated programmed death-ligand 1 (PD-L1), microsatellite instability/defective mismatch repair (MSI/dMMR), tumor mutational burden (TMB). MSI/dMMR is approved irrespective type, whereas PD-L1 certain (e.g., predicting response to first-line pembrolizumab monotherapy non-small cell lung cancer). Although not yet use, TMB been shown predict forms across multiple types. Less include tumor-infiltrating CD8+ lymphocytes specific gene signatures. Despite being investigated, assays MSI/dMMR, PD-L1, lack standardization still evolving. An urgent focus future research should be optimization method determining these biomarkers. SUMMARY Biomarkers paving way personalized treatment with diverse available biomarker an requirement.

Language: Английский

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Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer

Science Advances, Journal Year: 2020, Volume and Issue: 6(3)

Published: Jan. 16, 2020

While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder broader application of cancer immunotherapy. Here, we report a combinatorial approach that uses highly efficient tumor-selective gene carrier improve anticancer circumvent toxicity. In this study, engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers exhibit not only enhanced delivery capacity but also immune adjuvant properties by activating stimulator interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against checkpoint ligand PD-L1 immunostimulatory IL-2-encoding plasmid DNA hepatocellular carcinoma (HCC), increased tumoral infiltration activation CD8

Language: Английский

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WNT Signaling in Cancer Immunosurveillance

Trends in Cell Biology, Journal Year: 2018, Volume and Issue: 29(1), P. 44 - 65

Published: Sept. 13, 2018

Language: Английский

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Epigenetic modulation of antitumor immunity for improved cancer immunotherapy

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Dec. 20, 2021

Abstract Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also the activation, differentiation effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics cells impacting cell fate functionality, immunogenicity Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 STING, are regulated via epigenetic or/and cells, checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by tumor-associated stromal Thus, therapeutic strategies implementing modulating drugs expected significantly impact tumor microenvironment (TME) promoting transcriptional metabolic reprogramming local populations, resulting inhibition immunosuppressive (MDSCs Treg) activation anti-tumor T professional antigen presenting (APC), well which can serve non-professional APC. latter instance, agents may coordinately promote inducing de novo expression transcriptionally repressed antigens, increasing neoantigens MHC processing/presentation machinery, activating immunogenic death (ICD). ICD provides a rich source immunogens for cross-priming sensitizing interventional immunotherapy. way, modulators be envisioned effective components combination immunotherapy approaches capable mediating superior efficacy.

Language: Английский

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