TLR/WNT: A Novel Relationship in Immunomodulation of Lung Cancer

Martín-Medina, Aina; Cerón-Pisa, Noemi; Martinez-Font, Esther; Shafiek, Hanaa; Obrador‐Hevia, Antònia; Sauleda, Jaume; Iglesias, Amanda

doi:10.3390/ijms23126539

Cited by 14 publications

(7 citation statements)

References 123 publications

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“…TLR signaling pathways are involved in promoting cancer cell proliferation, invasion, and metastasis [8,28,29]. Activation of TLRs in NSCLC cells leads to upregulation of pro-inflammatory cytokines and chemokines (TNF-α or CCL2), contributing to the immunosuppressive nature of the tumor microenvironment [30][31][32][33][34][35][36]. TLRs (especially TLR4) have been shown to influence immune evasion mechanisms in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer

Smok-Kalwat,

Mertowska,

Mertowski

et al. 2024

JCM

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(1) Background: Non-small-cell lung cancer (NSCLC) represents a significant global health challenge, contributing to numerous cancer deaths. Despite advances in diagnostics and therapy, identifying reliable biomarkers for prognosis and therapeutic stratification remains difficult. Toll-like receptors (TLRs), crucial for innate immunity, now show potential as contributors to cancer development and progression. This study aims to investigate the role of TLR expression as potential biomarkers in the development and progression of NSCLC. (2) Materials and Methods: The study was conducted on 89 patients diagnosed with NSCLC and 40 healthy volunteers, for whom the prevalence of TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was assessed on selected subpopulations of T and B lymphocytes in the peripheral blood of recruited patients along with the assessment of their serum concentration. (3) Result: Our study showed several significant changes in NSCLC patients at the beginning of the study. This resulted in a 5-year follow-up of changes in selected TLRs in recruited patients. Due to the high mortality rate of NSCLC patients, only 16 patients survived the 5 years. (4) Conclusions: The results suggest that TLRs may constitute real biomarker molecules that may be used for future prognostic purposes in NSCLC. However, further validation through prospective clinical and functional studies is necessary to confirm their clinical utility. These conclusions may lead to better risk stratification and tailored interventions, benefiting NSCLC patients and bringing medicine closer to precision.

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Section: Discussionmentioning

confidence: 99%

Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer

Smok-Kalwat,

Mertowska,

Mertowski

et al. 2024

JCM

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“…Generally, WNT5A is an oncogenic protein involved in invasion and metastasis processes that increases its expression in human bronchial epithelial cells after exposure to cigarette smoke ( 92 , 93 ). At the same time, tobacco smoke could induce the expression of TLRs in macrophages becoming both a very potent inducer of lung cancer and a trigger factor contributing to the unbalancing of Wnt/TLR ( 94 , 95 ). TLRs have been discovered to be potential prognostic markers for lung cancer.…”

Section: Tlrs In Cancersmentioning

confidence: 99%

Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives

Mukherjee,

Patra,

Behzadi

et al. 2023

Front. Immunol.

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Toll-like receptors (TLRs) serve as the body’s first line of defense, recognizing both pathogen-expressed molecules and host-derived molecules released from damaged or dying cells. The wide distribution of different cell types, ranging from epithelial to immune cells, highlights the crucial roles of TLRs in linking innate and adaptive immunity. Upon stimulation, TLRs binding mediates the expression of several adapter proteins and downstream kinases, that lead to the induction of several other signaling molecules such as key pro-inflammatory mediators. Indeed, extraordinary progress in immunobiological research has suggested that TLRs could represent promising targets for the therapeutic intervention of inflammation-associated diseases, autoimmune diseases, microbial infections as well as human cancers. So far, for the prevention and possible treatment of inflammatory diseases, various TLR antagonists/inhibitors have shown to be efficacious at several stages from pre-clinical evaluation to clinical trials. Therefore, the fascinating role of TLRs in modulating the human immune responses at innate as well as adaptive levels directed the scientists to opt for these immune sensor proteins as suitable targets for developing chemotherapeutics and immunotherapeutics against cancer. Hitherto, several TLR-targeting small molecules (e.g., Pam3CSK4, Poly (I:C), Poly (A:U)), chemical compounds, phytocompounds (e.g., Curcumin), peptides, and antibodies have been found to confer protection against several types of cancers. However, administration of inappropriate doses of such TLR-modulating therapeutics or a wrong infusion administration is reported to induce detrimental outcomes. This review summarizes the current findings on the molecular and structural biology of TLRs and gives an overview of the potency and promises of TLR-directed therapeutic strategies against cancers by discussing the findings from established and pipeline discoveries.

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“…The Wnt ligands in the TME could interact and activate the TLR pathways. These TLR signalling mechanisms enhance the secretion of cytokines [20]. Inflammatory cytokines, such as interleukins and tumour necrosis factor (TNF), can create a pro-inflammatory environment that supports cancer development.…”

Section: Wnt-mediated Immune Editingmentioning

confidence: 99%

Navigating Tumour Microenvironment and Wnt Signalling Crosstalk: Implications for Advanced Cancer Therapeutics

Peri,

Narayanaa Y,

Hubert

et al. 2023

Cancers

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Cancer therapeutics face significant challenges due to drug resistance and tumour recurrence. The tumour microenvironment (TME) is a crucial contributor and essential hallmark of cancer. It encompasses various components surrounding the tumour, including intercellular elements, immune system cells, the vascular system, stem cells, and extracellular matrices, all of which play critical roles in tumour progression, epithelial–mesenchymal transition, metastasis, drug resistance, and relapse. These components interact with multiple signalling pathways, positively or negatively influencing cell growth. Abnormal regulation of the Wnt signalling pathway has been observed in tumorigenesis and contributes to tumour growth. A comprehensive understanding and characterisation of how different cells within the TME communicate through signalling pathways is vital. This review aims to explore the intricate and dynamic interactions, expressions, and alterations of TME components and the Wnt signalling pathway, offering valuable insights into the development of therapeutic applications.

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TLR/WNT: A Novel Relationship in Immunomodulation of Lung Cancer

Cited by 14 publications

References 123 publications

Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer

Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer

Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives

Navigating Tumour Microenvironment and Wnt Signalling Crosstalk: Implications for Advanced Cancer Therapeutics

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