IFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella

Lin, Qiubin; Li, Rong; Jia, Xian; Li, Renhao; Yu, Bin; Hu, Jingchu; Luo, Xiao-Jing; Badea, Smaranda; Chen, Xu; Fu, Gang; Lai, Kejiong; Lee, Ming-chun; Zhang, Baozhong; Gong, Hua‐Rui; Zhou, Nan; Chen, Xiao Lei; Lin, Shuhai; Huang, Jiandong

doi:10.1038/s41467-021-22755-3

Cited by 47 publications

(43 citation statements)

References 72 publications

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“…( Figure 1B , Supplementary Table 1 ). Overall, our results are in line with previous observation in Salmonella based tumor therapy, where Salmonella demonstrates an intrinsic anti-tumor effect, largely attributed to its immune stimulatory activity, as well as activation of both innate and adaptive immune cells ( 18 , 26 ).…”

Section: Resultssupporting

confidence: 92%

“…NGP plays a role as a negative regulator of tumor vascular development and metastasis ( 31 ) ( Figure 1B ). Proteins in Module 5 were also enriched in positive regulation of T cell proliferation ( 32 ). Proteins in Module 6 were involved in B cell receptor signaling pathway and immunoglobulin mediated immune response.…”

Section: Resultsmentioning

confidence: 99%

“…The development of a “perfect” bacteria strain for cancer therapy relies greatly on the understanding of host–bacteria interactions ( 32 ). Our tumor proteome profiling systematically revealed the dynamics of the tumor proteome after YB1 treatment, which can be beneficial for uncovering the underlying immunological mechanism of YB1-mediated tumor shrink.…”

Section: Discussionmentioning

confidence: 99%

“…Proteins in Module 5 were also enriched in positive regulation of T cell proliferation (32). Proteins in Module 6 were involved in B cell receptor signaling pathway and immunoglobulin mediated immune response.…”

Section: Key Immune Responses Revealed By K-means Clustering Analysismentioning

confidence: 99%

“…Systemic administration of Salmonella YB1 can effectively stimulate the immune system, resulting in the increased production of tumor necrosis factor-a (TNF-a), and interferon-g (IFN-g), as well as activation of both innate and adaptive immune cells (14)(15)(16)(17). These stimulated immune responses might create a hostile environment for tumor progression (18). However, the underlying systemic therapeutic mechanism of Salmonella YB1 remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Tumor Temporal Proteome Profiling Reveals the Immunological Triple Offensive Induced by Synthetic Anti-Cancer Salmonella

et al. 2021

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The engineered “obligate” anaerobic Salmonella typhimurium strain YB1 shows a prominent ability to repress tumor growth and metastasis, which has great potential as a novel cancer immunotherapy. However, the antitumor mechanism of YB1 remains unelucidated. To resolve the proteome dynamics induced by the engineered bacteria, we applied tumor temporal proteome profiling on murine bladder tumors after intravenous injection of either YB1 or PBS as a negative control. Our data suggests that during the two weeks treatment of YB1 injections, the cured tumors experienced three distinct phases of the immune response. Two days after injection, the innate immune response was activated, particularly the complement and blood coagulation pathways. In the meantime, the phagocytosis was initiated. The professional phagocytes such as macrophages and neutrophils were recruited, especially the infiltration of iNOS+ and CD68+ cells was enhanced. Seven days after injection, substantial amount of T cells was observed at the invasion margin of the tumor. As a result, the tumor shrunk significantly. Overall, the temporal proteome profiling can systematically reveal the YB1 induced immune responses in tumor, showing great promise for elucidating the mechanism of bacteria-mediated cancer immunotherapy.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Key Immune Responses Revealed By K-means Clustering Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor Temporal Proteome Profiling Reveals the Immunological Triple Offensive Induced by Synthetic Anti-Cancer Salmonella

et al. 2021

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A Customized Biohybrid Presenting Cascade Responses to Tumor Microenvironment

Li,

Zhu,

Zheng

et al. 2024

Advanced Materials

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Intrinsic characteristics of microorganisms, including non‐specific metabolism sites, toxic byproducts and uncontrolled proliferation constrain their exploitation in medical applications such as tumor therapy. Here, we report an engineered biohybrid that can efficiently target cancerous sites through a pre‐determined metabolic pathway to enable precise tumor ablation. In this system, DH5α Escherichia coli is engineered by the introduction of hypoxia‐inducible promoters and lactate oxidase genes, and further surface‐armored with iron‐doped ZIF‐8 nanoparticles. This bioengineered E. coli can produce and secrete lactate oxidase to reduce lactate concentration in response to hypoxic tumor microenvironment, as well as triggering immune activation. The peroxidase‐like functionality of the nanoparticles extends the end product of the lactate metabolism, enabling the conversion of hydrogen peroxide (H2O2) into highly cytotoxic hydroxyl radicals. This, coupled with the transformation of tirapazamine loaded on nanoparticles to toxic benzotriazinyl, culminates in severe tumor cell ferroptosis. Intravenous injection of this biohybrid significantly inhibited tumor growth and metastasis.This article is protected by copyright. All rights reserved

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Microbiota in Tumors: From Understanding to Application

Xie

Zhou

et al. 2022

Advanced Science

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Microbes with complex functions have been found to be a potential component in tumor microenvironments. Due to their low biomass and other obstacles, intratumor microbiota is poorly understood. Mucosal sites and normal adjacent tissues are important sources of intratumor microbiota, while hematogenous spread also leads to the invasion of microbes. Intratumor microbiota affects the progression of tumors through several mechanisms, such as DNA damage, activation of oncogenic pathways, induction of immunosuppression, and metabolization of drugs. Notably, in different types of tumors, the composition and abundance of intratumor microbiota are highly heterogeneous and may play different roles in the progression of tumors. Because of the concern in this field, several techniques such as omics and immunological methods have been used to study intratumor microbiota. Here, recent progress in this field is reviewed, including the potential sources of intratumor microbiota, their functions and related mechanisms, and their heterogeneity. Techniques that can be used to study intratumor microbiota are also discussed. Moreover, research is summarized into the development of strategies that can be used in antitumor treatment and prospects for possible future research in this field.

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IFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella

Cited by 47 publications

References 72 publications

Tumor Temporal Proteome Profiling Reveals the Immunological Triple Offensive Induced by Synthetic Anti-Cancer Salmonella

Tumor Temporal Proteome Profiling Reveals the Immunological Triple Offensive Induced by Synthetic Anti-Cancer Salmonella

A Customized Biohybrid Presenting Cascade Responses to Tumor Microenvironment

Microbiota in Tumors: From Understanding to Application

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