Systemic immune responses to irradiated tumours via the transport of antigens to the tumour periphery by injected flagellate bacteria

Wang, Wenguang; Xu, Haiheng; Ye, Qingsong; Tao, Feng; Wheeldon, Ian; Yuan, Ahu; Hu, Yiqiao; Wu, Jinhui

doi:10.1038/s41551-021-00834-6

Cited by 106 publications

(94 citation statements)

References 60 publications

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“…Vaccine delivery based on the antigenic action of the microbiota may significantly inhibit tumor-associated microorganisms, such as H. pylori , which possesses a variety of bacterial toxins and proteins, and can serve as key candidates for H. pylori vaccine construction ( 151 ). Following radiation therapy, intratumoral injection of genetically attenuated Salmonella strains coated with antigen-adsorbing cationic polymer nanoparticles resulted in tumor antigen accumulation around the tumor ( 152 ). This enhances crosstalk between antigens and DCs, and the use of flagellated bacteria to transport tumor antigens around tumors to enhance DC activation may open up new strategies for in situ cancer vaccination ( 152 ).…”

Section: Applications Of Microorganisms: a New Strategy To Improve Ca...mentioning

confidence: 99%

“…Following radiation therapy, intratumoral injection of genetically attenuated Salmonella strains coated with antigen-adsorbing cationic polymer nanoparticles resulted in tumor antigen accumulation around the tumor ( 152 ). This enhances crosstalk between antigens and DCs, and the use of flagellated bacteria to transport tumor antigens around tumors to enhance DC activation may open up new strategies for in situ cancer vaccination ( 152 ). In cytokine therapy, beneficial commensal microorganisms, AKK, combined with IL-2, can enhance the antitumor efficacy of IL-2 and enhance immune surveillance.…”

Section: Applications Of Microorganisms: a New Strategy To Improve Ca...mentioning

confidence: 99%

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Microbiome in cancer: An exploration of carcinogenesis, immune responses and immunotherapy

Zhou

Wang

et al. 2022

Front. Immunol.

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Cancer is a major disease endangering human health. More and more studies have shown that microorganisms play an extremely important role in the occurrence, development and treatment of tumors. As a very promising tumor treatment strategy, immunotherapy has also been proved to have a great relationship with microorganisms. Here, the authors review the contribution of the microbiota to cancer and the research on its impact on cancer immunotherapy. We also highlight the possible mechanism of their interaction and outlined the potential application of microbiota in tumor immunotherapy.

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Section: Applications Of Microorganisms: a New Strategy To Improve Ca...mentioning

confidence: 99%

Section: Applications Of Microorganisms: a New Strategy To Improve Ca...mentioning

confidence: 99%

Microbiome in cancer: An exploration of carcinogenesis, immune responses and immunotherapy

Zhou

Wang

et al. 2022

Front. Immunol.

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“…Recently, bacteria-mediated antitumor therapy has attracted extensive attention because of its natural tumor targeting ability and multiple immune activation properties. , With surface modification or genetic engineering, these tumor-targeting microorganisms can deliver or generate therapeutic substances in tumors to enhance the efficacy of various treatments including chemotherapy, radiotherapy, phototherapy, and so on. − More importantly, after entering tumor tissue, both live and inactivated bacteria could induce and strengthen innate immunity and adaptive immunity in a multidimensional manner to change the tumor immune microenvironment . Toll-like receptors of natural immune cells could identify pathogen-associated molecular patterns (PAMPs) on bacteria, accelerating cellular phagocytosis and destroying invading bacteria .…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic Immunomodulatory Functions of Radioactive Inactivated Bacterial Vectors for Enhanced Cancer Radio-immunotherapy

et al. 2022

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Biomaterial-based pleiotropic immune activation may effectively improve the response rate of immunotherapy and enhance the therapeutic effect of the tumor. Bacteria as a natural carrier have demonstrated great advantages in tumor targeted delivery and immune activation of the body. Herein, we construct an inactivated bacteria vector with 125 I/ 131 I labeling ( 125 I-VNP/ 131 I-VNP), which could retain radioiodine at the tumor site for a long time and deliver it into tumor cells and a tumor-associated macrophage (TAM), thus achieving efficient internal radioisotope therapy (IRT) of the primary tumor with good biosafety. More importantly, 131 I-VNP-mediated local IRT could further stimulate robust systemic antitumor immune responses via activation of the cGAS-STING pathway of innate immunity and promotion of the maturation of DC cells for T-cell-dominated adaptive immunity.After combination with systemic checkpoint blockade therapy (αPD-L1), 131 I-VNP, which induces the up-regulation of PD-L1 expression in the distant tumor, could lead to the inhibition of in situ colon cancer and protection against tumor rechallenge. Our strategy pioneers the use of an inactivated bacteria vector as a bridge to cleverly connect radiotherapy and immunotherapy and provide an enlightening idea for radio-immunotherapy mediated by pleiotropic immune activation functions of bacterial vectors.

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“…First of all, dendritic cells (DCs), essential for antigen recognition and presentation, are typically dysfunctional and rare in TME 19,20 . Moreover, antigens cannot cross through the tumor stroma and may be quickly cleared by the tumor tissues 21 . Recruiting more DCs and restoring their function by immune factors or activators can partly solve above problems, whereas the immunosuppressive TME is di cult to reverse and will cause the dysfunction of DCs again 22,23 .…”

Section: Introductionmentioning

confidence: 99%

Bacterial Outer Membrane Vesicle Based Versatile Nanosystem Boosts the Efferocytosis Blockade Triggered Tumor-Specific Immunity

Zhuang

Wang

Nie

et al. 2022

Preprint

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Efferocytosis inhibition is emerging as an attractive strategy for antitumor immune therapy because of the subsequent leak of abundant immunogenic contents. However, the practical efficacy is seriously impeded by the immunosuppressive tumor microenvironments. Here, we construct a versatile nanosystem that can not only inhibit the efferocytosis but also boost the following antitumor immunity. UNC2025 is loaded into the bacterial outer membrane vesicles (OMVs), which are then modified with maleimide (Mal). The prepared mU@OMVs effectively inhibits the efferocytosis by promoting the uptake while preventing the MerTK phosphorylation of tumor associated macrophages, and then captures the released TAAs through forming universal thioether bonds. The obtained in situ vaccine effectively transfers to LNs with by virtue of the intrinsic features of OMVs, and then provokes intense immune responses that can efficiently prevent the growth, metastasis and recurrence of tumors in mice, providing a novel strategy for cancer immunotherapy.

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Systemic immune responses to irradiated tumours via the transport of antigens to the tumour periphery by injected flagellate bacteria

Cited by 106 publications

References 60 publications

Microbiome in cancer: An exploration of carcinogenesis, immune responses and immunotherapy

Microbiome in cancer: An exploration of carcinogenesis, immune responses and immunotherapy

Pleiotropic Immunomodulatory Functions of Radioactive Inactivated Bacterial Vectors for Enhanced Cancer Radio-immunotherapy

Bacterial Outer Membrane Vesicle Based Versatile Nanosystem Boosts the Efferocytosis Blockade Triggered Tumor-Specific Immunity

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