Toll-like receptors in breast cancer immunity and immunotherapy

Zhou, Joseph; Zhang, Lin; Liu, Siyao; DeRubeis, David; Zhang, Dekai

doi:10.3389/fimmu.2024.1418025

Front. Immunol.

2024

DOI: 10.3389/fimmu.2024.1418025

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Toll-like receptors in breast cancer immunity and immunotherapy

Joseph Zhou,

Lin Zhang,

Siyao Liu

et al.

Abstract: Toll-like receptors (TLRs) are a key family of pattern recognition receptors (PRRs) in the innate immune system. The activation of TLRs will not only prevent pathogen infection but also respond to damage-induced danger signaling. Increasing evidence suggests that TLRs play a critical role in breast cancer development and treatment. However, the activation of TLRs is a double-edged sword that can induce either pro-tumor activity or anti-tumor effect. The underlying mechanisms of these opposite effects of TLR si… Show more

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Cited by 3 publications

References 88 publications

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Multi-Drug Resistance and Breast Cancer Progression via Toll-Like Receptors (TLRs) Signaling

Pallathadka,

Khaleel,

Zwamel

et al. 2024

Cell Biochem Biophys

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Multi-Drug Resistance and Breast Cancer Progression via Toll-Like Receptors (TLRs) Signaling

Pallathadka,

Khaleel,

Zwamel

et al. 2024

Cell Biochem Biophys

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Can the Analysis of Toll-like Receptors (TLR) on NK and NKT-like Cells Improve Gastric Cancer Diagnostics and Treatment?

Kos,

Bojarski,

Mertowska

et al. 2024

Cancers

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Background/Objectives: The aim of this study was to determine the assessment of the percentage of NK and NKT-like cells expressing Toll-like receptors (TLR-2, TLR-3, TLR-4, and TLR-9) in patients with gastric cancer (GC) compared with healthy volunteers (HV) and to investigate differences according to cancer subtype. We also assessed TLR gene expression by RT-qPCR to assess whether TLRs could be diagnostic and prognostic biomarkers. Methods: The study included 86 patients with histologically confirmed gastric cancer and 30 healthy volunteers. Peripheral blood samples were collected from the participants, and TLR expression on NK and NKT-like cells was assessed by flow cytometry and RT-qPCR. The expression of TLR2, TLR3, TLR4, and TLR9 genes was assessed using genetic material derived from NK and NKT-like cells sourced from PBMC. The obtained results were statistically analyzed using Mann–Whitney U and Kruskal–Wallis tests, and the predictive ability of variables was assessed using ROC curve analysis. Results: A significantly higher expression of TLR receptors (TLR-2, TLR-3, TLR-4, and TLR-9) was found in patients with gastric cancer compared to healthy volunteers (p < 0.05). TLR expression also differed depending on the cancer subtype, and higher expression was observed in more advanced GC subtypes. RT-qPCR analysis showed significantly increased expression of TLR genes in the group of GC patients. ROC curves indicate a high ability of TLRs to differentiate between GC patients and healthy individuals. Conclusions: The expression of TLRs on NK and NKT-like cells is clearly increased in patients with gastric cancer, especially in more advanced subtypes of the tumor. The results suggest that TLRs could potentially be used as diagnostic and prognostic biomarkers and represent potential targets for immune therapies in GC. However, further studies are needed to determine the functional role of TLRs in disease progression and the possibility of their use in personalized treatment.

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SPP1 mRNA Expression Is Associated with M2 Macrophage Infiltration and Poor Prognosis in Triple-Negative Breast Cancer

Chen,

Chen

et al. 2024

CIMB

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(1): Triple-negative breast cancer (TNBC) is an especially aggressive form of breast cancer defined by a poor prognosis and a lack of effective treatment options. There is a pressing need for validated predictive and prognostic biomarkers to assist in making treatment decisions and improve the prognostic accuracy for patients with this challenging disease. (2): We analyzed the RNA-seq data from three TNBC tissue samples alongside their corresponding normal tissues. Gene set enrichment analysis (GSEA) identified potential pathways. Additionally, we examined SPP1 mRNA expression datasets available in the Kaplan–Meier plotter and investigated the SPP1 protein expression patterns in our own tissue microarray cohort via immunohistochemistry. (3): The results revealed that genes associated with the Toll-like receptor signaling pathway showed a significant increase in activity in TNBC tissues when compared to normal breast tissues. Furthermore, SPP1 expression was found to be elevated in the TCGA TNBC dataset and correlated with a poor prognosis. This pattern was corroborated at the protein level in our TNBC tissue cohort; however, SPP1 protein expression did not demonstrate a significant impact on survival. Notably, SPP1 mRNA expression was strongly linked to tumor-associated macrophages (TAMs), particularly the M2 macrophage subtype, indicating a substantial association in the context of TNBC. (4): Our research highlights the significance of SPP1 mRNA as a key prognostic indicator and a potential molecular responder for TNBC treatment utilizing targeted therapies that focus on Toll-like receptor signaling pathways.

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Toll-like receptors in breast cancer immunity and immunotherapy

Cited by 3 publications

References 88 publications

Multi-Drug Resistance and Breast Cancer Progression via Toll-Like Receptors (TLRs) Signaling

Multi-Drug Resistance and Breast Cancer Progression via Toll-Like Receptors (TLRs) Signaling

Can the Analysis of Toll-like Receptors (TLR) on NK and NKT-like Cells Improve Gastric Cancer Diagnostics and Treatment?

SPP1 mRNA Expression Is Associated with M2 Macrophage Infiltration and Poor Prognosis in Triple-Negative Breast Cancer

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