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Published on: January 7, 2019
The Chemokine System in Oncogenic Pathways Driven by Viruses: Perspectives for Cancer Immunotherapy
Géraldine Schlecht-Louf1, Claire Deback1, Françoise Bachelerie1
1Microbiome and Immunosurveillance, Université Paris-Saclay, INSERM, Inflammation, 92140 Paris, France.
Abstract:
Chemokines interact with glycosaminoglycans of the extracellular matrix and activate heptahelical cellular receptors that mainly consist of G Protein-Coupled Receptors and a few atypical receptors also with decoy activity. They are well-described targets of oncogenic pathways and key players in cancer development, invasiveness, and metastasis acting both at the level of cancer cells and cells of the tumor microenvironment. Hence, they can regulate cancer cell proliferation and survival and promote immune or endothelial cell migration into the tumor microenvironment. Additionally, oncogenic viruses display the potential of jeopardizing the chemokine system by encoding mimics of chemokines and receptors as well as several products such as oncogenic proteins or microRNAs that deregulate their human host transcriptome. Conversely, the chemokine system participates in the host responses that control the virus life cycle, knowing that most oncoviruses establish asymptomatic latent infections. Therefore, the deregulated expression and function of chemokines and receptors as a consequence of acquired or inherited mutations could bias oncovirus infection toward pro-oncogenic pathways. We here review these different processes and discuss the anticancer therapeutic potential of targeting chemokine availability or receptor activation, from signaling to decoy-associated functions, in combination with immunotherapies.
Insights
Chemokines and their receptors are crucial in cancer development and metastasis. Targeting these pathways, alongside immunotherapies, shows promise for novel anticancer treatments.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Chemokines interact with extracellular matrix glycosaminoglycans and activate cellular receptors, primarily G Protein-Coupled Receptors.
- These molecules are implicated in cancer development, invasiveness, and metastasis by influencing cancer cells and the tumor microenvironment.
- Oncogenic viruses can disrupt the chemokine system, while the system also plays a role in controlling viral infections.
Purpose of the Study:
- To review the multifaceted roles of the chemokine system in cancer.
- To discuss how oncogenic viruses interact with and potentially deregulate the chemokine system.
- To explore the therapeutic potential of targeting chemokine pathways in cancer treatment, especially in combination with immunotherapy.
Main Methods:
- Literature review of chemokine interactions, cancer pathways, and viral hijacking of the chemokine system.
- Analysis of the dual role of chemokines in cancer progression and host antiviral responses.
- Discussion of therapeutic strategies targeting chemokine availability and receptor activation.
Main Results:
- Chemokines regulate cancer cell proliferation, survival, and immune cell infiltration into tumors.
- Oncogenic viruses encode chemokine/receptor mimics and deregulate host gene expression, potentially promoting oncogenesis.
- Mutations in chemokine systems can predispose to pro-oncogenic viral infections.
Conclusions:
- Targeting chemokine availability or receptor activation offers therapeutic potential for cancer.
- Combining chemokine-targeting strategies with immunotherapies may enhance anticancer efficacy.
- Understanding chemokine system dysregulation is key for developing novel cancer treatments.
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