TLR1/TLR2 signaling blocks the suppression of monocytic myeloid-derived suppressor cell by promoting its differentiation into M1-type macrophage

Deng, Yuting; Jiao, Yang; Qian, Jiawen; Liu, Ronghua; Huang, Enyu; Wang, Yuedi; Luo, Fengming; Chu, Yiwei

doi:10.1016/j.molimm.2019.06.006

Cited by 37 publications

(26 citation statements)

References 41 publications

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“…In an animal model, TLR1/ TLR2 activation was found to be linked to a reduction in tumor growth and a selective downregulation of the M-MDSC subpopulation. The use of a TLR2 agonist exhibited a positive effect on M-MDSC redistribution toward M1 macrophages [102].…”

Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 97%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 97%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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“…To study whether TLR2 activation may promote anti-cancer immune responses, exogenous TLR2 ligands were administered in several murine cancer models. In lung cancer models, the administration of synthetic or bacterial-derived TLR2 ligands induces the differentiation of monocytic myeloid derived suppressor cells (M-MDSC) toward the anti-tumoral M1 phenotype, with the production of IFN-γ, nitric oxide (NO), and pro-inflammatory cytokines such as TNF-α, IL-12p40, and IL-12p70, suggesting a correlation between TLR2 activation and a better anti-tumor response [26,27]. The efficacy of TLR2 stimulation on tumor-infiltrated leukocytes was demonstrated also in a melanoma model.…”

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

confidence: 99%

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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“…Further, it has been shown that TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during ALI, and that TLR4 and TLR3 in macrophages are an important determinant in ALI (223), and that there is an association between respiratory syncytial virus TLR3-mediated immune responses and chronic obstructive pulmonary disease exacerbation frequency (224). TLR2 activation of macrophages leads to M1 polarization, and a shift from M2 into M1 macrophages (225). In addition, it has been shown that TLR2 activation of macrophages can impair activity of M2-like macrophages (226).…”

Section: Mycobacterium Obuense (Imm-101)mentioning

confidence: 99%

Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends”

et al. 2020

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The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends."

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TLR1/TLR2 signaling blocks the suppression of monocytic myeloid-derived suppressor cell by promoting its differentiation into M1-type macrophage

Cited by 37 publications

References 41 publications

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

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

Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends”

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