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Basic understanding and therapeutic approaches to target toll-like receptors in cancerous microenvironment and
Mojtaba Khajeh Alizadeh Attar1,2, Muhammad Ayaz Anwar3, Mahsa Eskian1,4,5
1Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Abstract:
Toll-like receptors (TLRs) are transmembrane components that sense danger signals, like damage- and pathogen-associated molecular pattern molecules, as receptors, and maintain homeostasis in tissues. They are mainly involved in immune system activation through a variety of mediators, which either carry out (1) elimination of pathogenic threats and redressing homeostatic imbalances or (2) contribution to the initiation and worsening of pathological conditions, including cancers. Under physiological conditions, TLRs coordinate the innate and adaptive immunity, and inhibit autoimmune disorders. In pathological conditions, such as cancer, they can present both tumor and receptor-specific roles. Although the roles of individual TLRs in various cancers have been described, the effects of targeting TLRs to treat cancer and prevent metastasis are still controversial. A growing body of literature has suggested contribution of both activators and inhibitors of TLR signaling pathway for cancer treatment, dependent on several context-specific factors. In short, TLRs can play dual roles with contradictory outcomes in neoplastic conditions. This hampers the development of TLR-based therapeutic interventions. A better understanding of the interwoven TLR pathways in cancerous microenvironment is necessary to design TLR-based therapies. In this review, we consider the molecular mechanisms of TLRs signaling and their involvement in tumor progression. Therapeutic modalities targeting TLRs for cancer treatment are discussed as well.
Insights
Toll-like receptors (TLRs) play dual roles in cancer, activating immunity or promoting tumor growth. Understanding TLR signaling in the tumor microenvironment is crucial for developing effective cancer therapies.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Toll-like receptors (TLRs) are key sensors of danger signals, crucial for maintaining tissue homeostasis and immune responses.
- TLRs orchestrate innate and adaptive immunity, inhibiting autoimmune disorders under physiological conditions.
- In cancer, TLRs exhibit complex, context-dependent roles, acting as both tumor promoters and suppressors.
Purpose of the Study:
- To review the molecular mechanisms of Toll-like receptor (TLR) signaling.
- To elucidate the involvement of TLRs in tumor progression and metastasis.
- To discuss current and potential therapeutic strategies targeting TLRs for cancer treatment.
Main Methods:
- Literature review of molecular mechanisms of TLR signaling.
- Analysis of TLR involvement in various cancer types and stages.
- Evaluation of therapeutic interventions targeting TLRs in preclinical and clinical settings.
Main Results:
- TLRs can either eliminate threats and restore homeostasis or contribute to cancer initiation and progression.
- The dual role of TLRs in neoplastic conditions complicates the development of targeted therapies.
- Both activators and inhibitors of TLR signaling pathways show potential in cancer treatment, depending on context.
Conclusions:
- A deeper understanding of TLR signaling within the tumor microenvironment is essential for effective cancer therapy development.
- Targeting TLRs offers promising therapeutic avenues, but requires careful consideration of context-specific factors.
- Further research is needed to harness the immunomodulatory potential of TLRs for cancer treatment and metastasis prevention.
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