Dual roles of myeloid‑derived suppressor cells induced by Toll‑like receptor signaling in cancer (Review)

Zhou, Hongyue; Jiang, Mengyu; Yuan, Hongyan; Ni, Weihua; Tai, Guihua

doi:10.3892/ol.2020.12410

Cited by 27 publications

(25 citation statements)

References 100 publications

(155 reference statements)

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“…For TAMs, this includes producing anti-inflammatory mediators such as IL-10, Arg1, and TGF-b (56)(57)(58), promoting the expression of checkpoint inhibitors to suppress T cells (56,57), inducing cancer stem cell proliferation via IL-6 signaling through STAT3 (59), and producing VEGF to stimulate angiogenesis (60,61). These effects are also seen in TANs and MDSCs, which have both been shown to produce similar profiles of cytokines, checkpoint inhibitors, and growth factors (47,48,(62)(63)(64).…”

Section: The Tumor Microenvironment and Tumor Associated Immune Cellsmentioning

confidence: 99%

Immunological Effects of Histotripsy for Cancer Therapy

et al. 2021

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Cancer is the second leading cause of death worldwide despite major advancements in diagnosis and therapy over the past century. One of the most debilitating aspects of cancer is the burden brought on by metastatic disease. Therefore, an ideal treatment protocol would address not only debulking larger primary tumors but also circulating tumor cells and distant metastases. To address this need, the use of immune modulating therapies has become a pillar in the oncology armamentarium. A therapeutic option that has recently emerged is the use of focal ablation therapies that can destroy a tumor through various physical or mechanical mechanisms and release a cellular lysate with the potential to stimulate an immune response. Histotripsy is a non-invasive, non-ionizing, non-thermal, ultrasound guided ablation technology that has shown promise over the past decade as a debulking therapy. As histotripsy therapies have developed, the full picture of the accompanying immune response has revealed a wide range of immunogenic mechanisms that include DAMP and anti-tumor mediator release, changes in local cellular immune populations, development of a systemic immune response, and therapeutic synergism with the inclusion of checkpoint inhibitor therapies. These studies also suggest that there is an immune effect from histotripsy therapies across multiple murine tumor types that may be reproducible. Overall, the effects of histotripsy on tumors show a positive effect on immunomodulation.

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Section: The Tumor Microenvironment and Tumor Associated Immune Cellsmentioning

confidence: 99%

Immunological Effects of Histotripsy for Cancer Therapy

et al. 2021

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“…The differences in the direction of action, apparently, could be explained by the introduction in vivo of not only the TLR9 agonist (CpG ODN), but also of the NOD2 agonist (IFA) or, in the second experiment, an additional viral protein acting on the TLR surface receptors. It has been shown that TLR agonists can both activate the immunosuppressive activity of MDSCs and block it [17]. Molecular mechanisms of regulating MDSCs by TLR are still relatively limited.…”

Section: Discussionmentioning

confidence: 99%

“…One of the possible approaches to blocking the negative effect of MDSCs on immune response is to influence the toll-like receptor (TLR) signaling that is involved in MDSC regulation [17]. TLR agonists can modulate the suppressive function of MDSCs [18].…”

Section: Introductionmentioning

confidence: 99%

Difluoromethylornithine (DFMO), an Inhibitor of Polyamine Biosynthesis, and Antioxidant N-Acetylcysteine Potentiate Immune Response in Mice to the Recombinant Hepatitis C Virus NS5B Protein

Леснова

Масалова

Permyakova

et al. 2021

IJMS

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Hepatitis C virus (HCV) is one of the main triggers of chronic liver disease. Despite tremendous progress in the HCV field, there is still no vaccine against this virus. Potential vaccines can be based on its recombinant proteins. To increase the humoral and, especially, cellular immune response to them, more effective adjuvants are needed. Here, we evaluated a panel of compounds as potential adjuvants using the HCV NS5B protein as an immunogen. These compounds included inhibitors of polyamine biosynthesis and urea cycle, the mTOR pathway, antioxidants, and cellular receptors. A pronounced stimulation of cell proliferation and interferon-γ (IFN-γ) secretion in response to concanavalin A was shown for antioxidant N-acetylcysteine (NAC), polyamine biosynthesis inhibitor 2-difluoromethylornithine (DFMO), and TLR9 agonist CpG ODN 1826 (CpG). Their usage during the immunization of mice with the recombinant NS5B protein significantly increased antibody titers, enhanced lymphocyte proliferation and IFN-γ production. NAC and CpG decreased relative Treg numbers; CpG increased the number of myeloid-derived suppressor cells (MDSCs), whereas neither NAC nor DFMO affected MDSC counts. NAC and DFMO suppressed NO and interleukin 10 (IL-10) production by splenocytes, while DFMO increased the levels of IL-12. This is the first evidence of immunomodulatory activity of NAC and DFMO during prophylactic immunization against infectious diseases.

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“…Several studies have reported that the survival, differentiation, and immunosuppressive activity of MDSCs are affected by different Toll-like receptors (TLRs) 59 . Activation of TLR-4 by BCG 60 and Immunomax ® immunostimulant 61 decreased MDSCs frequency, whereas stimulation of TLR-7/8 by Imiquimod switched the anti-inflammatory profile of MDSC to a pro-inflammatory and antitumoral profile 62 .…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-suppressive activity over T-cell proliferation and fungal clearance in a murine model of Fonsecaea pedrosoi infection

Breda

Kaihami

et al. 2021

Sci Rep

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Neutrophils are essential to control several fungal infections. These cells are commonly known for their pro-inflammatory activities. However, some studies have demonstrated the anti-inflammatory properties of neutrophils during certain infectious diseases, culminating in the inhibition of T cell proliferation. Chromoblastomycosis (CBM) is a deep and progressive mycosis that affects thousands of people worldwide. Although neutrophil infiltrates are observed in the lesion histopathology, the fungus can overtake the immune system response and destroy the host-infected tissue. The present study demonstrated that neutropenic animals had an increase in the IL-6 production in the spleen and liver, followed by a lower fungal burden in these organs up to 14 days of infection. Neutropenic animals also showed a lower F. pedrosoi-specific antibody production 14-days post infection and higher T-cell proliferation in the in vitro experiments after stimulation with F. pedrosoi-purified proteins. Taken together, our results suggest that the presence of regulatory neutrophils in the mouse model of F. pedrosoi infection could act favoring the spread of the fungus and the chronicity of the infection. These findings shed light on the CBM treatment, which might target neutrophil polarization as a new therapy approach to treat CBM lesions.

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Dual roles of myeloid‑derived suppressor cells induced by Toll‑like receptor signaling in cancer (Review)

Cited by 27 publications

References 100 publications

Immunological Effects of Histotripsy for Cancer Therapy

Immunological Effects of Histotripsy for Cancer Therapy

Difluoromethylornithine (DFMO), an Inhibitor of Polyamine Biosynthesis, and Antioxidant N-Acetylcysteine Potentiate Immune Response in Mice to the Recombinant Hepatitis C Virus NS5B Protein

Neutrophil-suppressive activity over T-cell proliferation and fungal clearance in a murine model of Fonsecaea pedrosoi infection

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