Targeting chemokines/chemokine receptors: a promising strategy for enhancing the immunotherapy of pancreatic ductal adenocarcinoma

Gong, Ruining; Ren, He

doi:10.1038/s41392-020-00267-8

Cited by 13 publications

(4 citation statements)

References 5 publications

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“…The TME comprises extracellular matrix (ECM), cancerous cells and non-cancerous cells including (mainly) pro-tumorigenic stromal, immune and endothelial cells. The cancerous cells release pro-tumorigenic chemokines, such as C-X-C motif chemokine ligand (CXCL)12, and pro-tumorigenic cytokines, including interleukin (IL)-6, IL-8, IL-10, transforming growth factor-beta (TGF-β), macrophage colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF) [14,15]. Abundant release of these molecules sways the immune balance from effective immune surveillance to immune tolerance by activating regulatory T cells (Tregs), tumor-associated macrophages (TAMs), T-helper2 (Th2) cells and myeloid-derived suppressor cells (MDSCs).…”

Section: Mechanisms Of Immune Evasionmentioning

confidence: 99%

Pancreatic Cancer and Immunotherapy: A Clinical Overview

Timmer

Geboers

Nieuwenhuizen

et al. 2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high mortality. The vast majority of patients present with unresectable, advanced stage disease, for whom standard of care chemo(radio)therapy may improve survival by several months. Immunotherapy has led to a fundamental shift in the treatment of several advanced cancers. However, its efficacy in PDAC in terms of clinical benefit is limited, possibly owing to the immunosuppressive, inaccessible tumor microenvironment. Still, various immunotherapies have demonstrated the capacity to initiate local and systemic immune responses, suggesting an immune potentiating effect. In this review, we address PDAC’s immunosuppressive tumor microenvironment and immune evasion methods and discuss a wide range of immunotherapies, including immunomodulators (i.e., immune checkpoint inhibitors, immune stimulatory agonists, cytokines and adjuvants), oncolytic viruses, adoptive cell therapies (i.e., T cells and natural killer cells) and cancer vaccines. We provide a general introduction to their working mechanism as well as evidence of their clinical efficacy and immune potentiating abilities in PDAC. The key to successful implementation of immunotherapy in this disease may rely on exploitation of synergistic effects between treatment combinations. Accordingly, future treatment approaches should aim to incorporate diverse and novel immunotherapeutic strategies coupled with cytotoxic drugs and/or local ablative treatment, targeting a wide array of tumor-induced immune escape mechanisms.

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Section: Mechanisms Of Immune Evasionmentioning

confidence: 99%

Pancreatic Cancer and Immunotherapy: A Clinical Overview

Timmer

Geboers

Nieuwenhuizen

et al. 2021

Cancers

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“…1,2 Overexpression of EGFR or amplification of the EGFR gene or its mutation and rearrangement led to a number of cancers in various organs and malignancies. 3–7…”

Section: Introductionmentioning

confidence: 99%

Identification of natural flavonoids as novel EGFR inhibitors using DFT, molecular docking, and molecular dynamics

Sepay¹,

Mondal²,

Al-Muhanna³

et al. 2022

New J. Chem.

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“…The authors claimed that this observation suggests that HCC patients treated with either macrophage-targeted therapy or immune checkpoint inhibitors will not have an illicit off-target immune response in the remaining non-cancerous tissue infected with HBV [41]. What appears certain from this study, and others, is that targeting the TAM chemokine axis can enhance the effect of immune checkpoint inhibitors by recruiting and activating more CD8 + and CD4 + T cells, which increases the number of tumor-infiltrating lymphocytes and makes the microenvironment less immunosuppressive [42][43][44][45].…”

Section: Use Of Cytometry By Time-of-flight For Characterization Of M...mentioning

confidence: 70%

Cutting-Edge Platforms for Analysis of Immune Cells in the Hepatic Microenvironment—Focus on Tumor-Associated Macrophages in Hepatocellular Carcinoma

Millian

Saldarriaga

Wanninger

et al. 2022

Cancers

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The role of tumor-associated macrophages (TAMs) in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. Most studies rely on platforms that remove intrahepatic macrophages from the microenvironment prior to evaluation. Cell isolation causes activation and phenotypic changes that may not represent their actual biology and function in situ. State-of-the-art methods provides new strategies to study TAMs without losing the context of tissue architecture and spatial relationship with neighboring cells. These technologies, such as multispectral imaging (e.g., Vectra Polaris), mass cytometry by time-of-flight (e.g., Fluidigm CyTOF), cycling of fluorochromes (e.g., Akoya Biosciences CODEX/PhenoCycler-Fusion, Bruker Canopy, Lunaphore Comet, and CyCIF) and digital spatial profiling or transcriptomics (e.g., GeoMx or Visium, Vizgen Merscope) are being utilized to accurately assess the complex cellular network within the tissue microenvironment. In cancer research, these platforms enable characterization of immune cell phenotypes and expression of potential therapeutic targets, such as PDL-1 and CTLA-4. Newer spatial profiling platforms allow for detection of numerous protein targets, in combination with whole transcriptome analysis, in a single liver biopsy tissue section. Macrophages can also be specifically targeted and analyzed, enabling quantification of both protein and gene expression within specific cell phenotypes, including TAMs. This review describes the workflow of each platform, summarizes recent research using these approaches, and explains the advantages and limitations of each.

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Targeting chemokines/chemokine receptors: a promising strategy for enhancing the immunotherapy of pancreatic ductal adenocarcinoma

Cited by 13 publications

References 5 publications

Pancreatic Cancer and Immunotherapy: A Clinical Overview

Pancreatic Cancer and Immunotherapy: A Clinical Overview

Identification of natural flavonoids as novel EGFR inhibitors using DFT, molecular docking, and molecular dynamics

Cutting-Edge Platforms for Analysis of Immune Cells in the Hepatic Microenvironment—Focus on Tumor-Associated Macrophages in Hepatocellular Carcinoma

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