In vivo anti- and pro-tumour activities of the TLR2 ligand FSL-1

Kiura, Kazuto; Hasebe, Akira; Saeki, Ayumi; Segawa, Taku; Okada, Futoshi; Shamsul, Haque Mohammad; Ohtani, Makoto; Into, Takeshi; Inoue, Nozomu; Wakita, Minoru; Shibata, Ken Ichiro

doi:10.1016/j.imbio.2011.02.006

Cited by 10 publications

(8 citation statements)

References 39 publications

(70 reference statements)

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“…This effect was reverted by the combined administration of anti-CD25 antibodies, suggesting the involvement of Tregs in the FSL-1 pro-tumoral effect. None of these effects was observed in TLR2 −/− mice, confirming that both pro-and anti-tumor effects are TLR2-dependent [29]. TLR2 seems to play a role also in NK cell-mediated anti-tumor immunity.…”

Section: The Role Of Tlr2 In Anti-tumor Immune Responsementioning

confidence: 65%

Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota

Lorenzo

Bolli

Tarone

et al. 2020

IJMS

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Toll-like receptor 2 (TLR2) expressed on myeloid cells mediates the recognition of harmful molecules belonging to invading pathogens or host damaged tissues, leading to inflammation. For this ability to activate immune responses, TLR2 has been considered a player in anti-cancer immunity. Therefore, TLR2 agonists have been used as adjuvants for anti-cancer immunotherapies. However, TLR2 is also expressed on neoplastic cells from different malignancies and promotes their proliferation through activation of the myeloid differentiation primary response protein 88 (MyD88)/nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway. Furthermore, its activation on regulatory immune cells may contribute to the generation of an immunosuppressive microenvironment and of the pre-metastatic niche, promoting cancer progression. Thus, TLR2 represents a double-edge sword, whose role in cancer needs to be carefully understood for the setup of effective therapies. In this review, we discuss the divergent effects induced by TLR2 activation in different immune cell populations, cancer cells, and cancer stem cells. Moreover, we analyze the stimuli that lead to its activation in the tumor microenvironment, addressing the role of danger, pathogen, and microbiota-associated molecular patterns and their modulation during cancer treatments. This information will contribute to the scientific debate on the use of TLR2 agonists or antagonists in cancer treatment and pave the way for new therapeutic avenues.

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Section: The Role Of Tlr2 In Anti-tumor Immune Responsementioning

confidence: 65%

Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota

Lorenzo

Bolli

Tarone

et al. 2020

IJMS

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“…As underlined by Mele and Madrenas [192] and supported by other studies [171], it is clear that TLR2 plays both proinflammatory and regulatory roles and that through TLR2 activation, alone or in combination with other stimuli, both effector and regulatory immune mechanisms can be elicited in vivo depending on not yet completely clarified factors. To focus on understanding these discrepancies should be a priority for rationally exploring TLR2 stimulation in vaccine development.…”

Section: Immunomodulation By Formulations Targeting Tlr2mentioning

confidence: 65%

Targeting TLR2 for Vaccine Development

Basto

Leitão

2014

Journal of Immunology Research

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Novel and more effective immunization strategies against many animal diseases may profit from the current knowledge on the modulation of specific immunity through stimulation of innate immune receptors. Toll-like receptor (TLR)2-targeting formulations, such as synthetic lipopeptides and antigens expressed in fusion with lipoproteins, have been shown to have built-in adjuvant properties and to be effective at inducing cellular and humoral immune mechanisms in different animal species. However, contradictory data has arisen concerning the profile of the immune response elicited. The benefits of targeting TLR2 for vaccine development are thus still debatable and more studies are needed to rationally explore its characteristics. Here, we resume the main features of TLR2 and TLR2-induced immune responses, focusing on what has been reported for veterinary animals.

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“…We have previously shown that the TLR2 ligand FSL‐1, but not the TLR9 ligand CpG‐DNA, enhanced the growth of nTreg cells isolated from murine spleens (Kiura et al ., ). Therefore, an experiment was carried out to investigate whether heat‐killed cells of Sg‐wt and Sg‐dLP enhanced the proliferation of nTreg cells isolated from splenocytes of TLR2 +/+ or TLR2 −/− mice and the proliferation of CD4 + CD25 − T cells (Th cells) prepared during the isolation process of nTreg cells.…”

Section: Resultsmentioning

confidence: 97%

“…We have previously demonstrated that the TLR2 ligand FSL‐1 reduced the activity of nTreg cells to suppress the proliferation of Th cells triggered by anti‐CD3ε (Kiura et al ., ). Therefore, an experiment was carried out to determine whether Sm‐wt, Sm‐dLP, Sg‐wt and Sg‐dLP affect the suppressive activity of nTreg cells.…”

Section: Resultsmentioning

confidence: 97%

Toll‐like receptor 2‐mediated modulation of growth and functions of regulatory T cells by oral streptococci

Saeki

Segawa

Abe

et al. 2013

Molecular Oral Microbiology

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This study was designed to determine whether oral streptococci modulate the growth and functions of regulatory T cells. Heat-killed cells of wild-type strains of Streptococcus gordonii and Streptococcus mutans induced the Toll-like receptor 2 (TLR2) -mediated nuclear factor-κB (NF-κB) activation, but their lipoprotein-deficient strains did not. Stimulation with these streptococci resulted in a significant increase in the frequency of CD4(+) CD25(+) Foxp3(+) regulatory T cells in splenocytes derived from both TLR2(+/+) and TLR2(-/-) mice, but the level of increase in TLR2(+/+) splenocytes was stronger than that in TLR2(-/-) splenocytes. Both strains of S. gordonii enhanced the proliferation of CD4(+) CD25(+) Foxp3(+) regulatory T cells isolated from TLR2(+/+) mice at the same level as those from TLR2(-/-) mice in an interleukin-2-independent manner. However, wild-type and lipoprotein-deficient strains of both streptococci did not enhance the suppressive activity of the isolated regulatory T cells in vitro, but rather inhibited it. TLR ligands also inhibited the suppressive activity of the regulatory T cells. Inhibition of the suppressive activity was recovered by the addition of anti-IL-6 antibody. Pretreatment of antigen-presenting cells with the NF-κB inhibitor BAY11-7082 enhanced the suppressive activity of the regulatory T cells. These results suggested that interleukin-6 produced by antigen-presenting cells inhibits the suppressive activity of the regulatory T cells. Wild-type strain, but not lipoprotein-deficient strain, of S. gordonii reduced the frequency of CD4(+) CD25(+) Foxp3(+) regulatory T cells in the acute infection model, whereas both strains of S. gordonii increased it in the chronic infection model mice. Hence, this study suggests that oral streptococci are capable of modulating the growth and functions of regulatory T cells in vitro and in vivo.

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In vivo anti- and pro-tumour activities of the TLR2 ligand FSL-1

Cited by 10 publications

References 39 publications

Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota

Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota

Targeting TLR2 for Vaccine Development

Toll‐like receptor 2‐mediated modulation of growth and functions of regulatory T cells by oral streptococci

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