Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling

Shi, Yi; Zheng, Wenxin; Yang, Kaiting; Harris, Katharine G.; Ni, Kaiyuan; Xue, Li; Lin, Wenbin; Chang, Eugene B.; Weichselbaum, Ralph R.; Fu, Yang–Xin

doi:10.1084/jem.20192282

Cited by 220 publications

(210 citation statements)

References 35 publications

(57 reference statements)

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“… 245 Microbiota ( Bifidobacterium ) accumulated in colon adenocarcinoma promotes immunotherapy by activating STING signaling. 246 Nejman et al 247 demonstrated that bacteria are present in cancer or immune cells, further confirming the presence of microbiomes in TME, although its role remains unknown. This area is largely unknown, and the definition of microbiome microenvironment requires consensus.…”

Section: Discussion and Outlookmentioning

confidence: 93%

The updated landscape of tumor microenvironment and drug repurposing

Jin

2020

Sig Transduct Target Ther

701

483

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Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods. Herein, we present an updated image of TME with emphasis on hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, and mechanical microenvironment. We then summarize conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, and statin in new antitumor application. These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice. We also provide our outlook on directions and potential applications of TME theory. This review depicts a comprehensive and vivid landscape of TME from biology to treatment.

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Section: Discussion and Outlookmentioning

confidence: 93%

The updated landscape of tumor microenvironment and drug repurposing

Jin

2020

Sig Transduct Target Ther

701

483

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“…Bifidobacterium (Shi et al, 2020) N/A Pancreatic ductal adenocarcinoma microenvironments that promote tumor initiation and progression (Belkaid and Hand, 2014;Garrett, 2015). Many studies have shown that dysbiosis in local bacterial communities can cause a chronic, pro-inflammatory immune response, and thereby promote cancer growth.…”

Section: Proposed Mechanismmentioning

confidence: 99%

“…Yu et al showed that F. nucleatum promotes chemoresistance by activation autophagy pathway through downregulation of microRNAs (miR-18a and miR4802) (Yu et al, 2017). In another study that investigated the role of intratumor microbiota in CD47-based cancer immunotherapy, Shi et al found that colonic Bifidobacterium accumulates in tumor sites and facilitates local anti-CD47 treatment via the STING pathway (Shi et al, 2020).…”

Section: Colorectal Cancermentioning

confidence: 99%

Unexpected guests in the tumor microenvironment: microbiome in cancer

et al. 2020

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Although intestinal microbiome have been established as an important biomarker and regulator of cancer development and therapeutic response, less is known about the role of microbiome at other body sites in cancer. Emerging evidence has revealed that the local microbiota make up an important part of the tumor microenvironment across many types of cancer, especially in cancers arising from mucosal sites, including the lung, skin and gastrointestinal tract. The populations of bacteria that reside specifically within tumors have been found to be tumor-type specific, and mechanistic studies have demonstrated that tumor-associated microbiota may directly regulate cancer initiation, progression and responses to chemo- or immuno-therapies. This review aims to provide a comprehensive review of the important literature on the microbiota in the cancerous tissue, and their function and mechanism of action in cancer development and treatment.

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“…Cancer immunotherapy, the strategy focusing on inhibition of immunosuppressive pathways and activation of immunostimulatory pathways, is becoming an important treatment modality alongside surgery, radiotherapy, and chemotherapy for certain cancers. 21,39 The history of cancer immunotherapy traces back to the late nineteenth century, where William Coley, an American bone surgeon, found that intratumoral injections of killed bacteria presented anti-tumor therapeutic effects. 40 The so-called "Coley's Toxin" was a promising outcome as monotherapy with 50% of total 104 patients with soft-tissue sarcoma showing complete tumor regression and more than 5year survival.…”

Section: Cancer and Cancer Immunotherapymentioning

confidence: 99%

Nanoscale Metal–Organic Frameworks for Cancer Immunotherapy

et al. 2020

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Conspectus Cancer immunotherapy, particularly checkpoint blockade immunotherapy (CBI), has revolutionized the treatment of some cancers by reactivating the antitumor immunity of hosts with durable response and manageable toxicity. However, many cancer patients with low tumor antigen exposure and immunosuppressive tumor microenvironments do not respond to CBI. A variety of methods have been investigated to reverse immunosuppressive tumor microenvironments and turn “cold” tumors “hot” with the goal of extending the therapeutic benefits of CBI to a broader population of cancer patients. Immunostimulatory adjuvant treatments, such as cancer vaccines, photodynamic therapy (PDT), radiotherapy (RT), radiotherapy–radiodynamic therapy (RT-RDT), and chemodynamic therapy (CDT), promote antigen presentation and T cell priming and, when used in combination with CBI, reactivate and sustain systemic antitumor immunity. Cancer vaccines directly provide tumor antigens, while immunoadjuvant therapies such as PDT, RT, RT-RDT, and CDT kill cancer cells in an immunogenic fashion to release tumor antigens in situ. Direct administration of tumor antigens or indirect intratumoral immunoadjuvant therapies as in situ cancer vaccines initiate the immuno-oncology cycle for antitumor immune response. With the rapid growth of cancer nanotechnology in the past two decades, a large number of nanoparticle platforms have been studied, and some nanomedicines have been translated into clinical trials. Nanomedicine provides a promising strategy to enhance the efficacy of immunoadjuvant therapies to potentiate cancer immunotherapy. Among these nanoparticle platforms, nanoscale metal–organic frameworks (nMOFs) have emerged as a unique class of porous hybrid nanomaterials with metal cluster secondary building units and organic linkers. With molecular modularity, structural tunability, intrinsic porosity, tunable stability, and biocompatibility, nMOFs are ideally suited for biomedical applications, particularly cancer treatments. In this Account, we present recent breakthroughs in the design of nMOFs as nanocarriers for cancer vaccine delivery and as nanosensitizers for PDT, CDT, RT, and RT-RDT. The versatility of nMOFs allows them to be fine-tuned to effectively load tumor antigens and immunoadjuvants as cancer vaccines and significantly enhance the local antitumor efficacy of PDT, RT, RT-RDT, and CDT via generation of reactive oxygen species (ROS) for in situ cancer vaccination. These nMOF-based treatments are further combined with cancer immunotherapies to elicit systemic antitumor immunity. We discuss novel strategies to enhance light tissue penetration and overcome tumor hypoxia in PDT, to increase energy deposition and ROS diffusion in RT, to combine the advantages of PDT and RT to enable RT-RDT, and to trigger CDT by hijacking aberrant metabolic processes in tumors. Loading nMOFs with small-molecule drugs such as an indoleamine 2,3-dioxygenase inhibitor, the toll-like receptor agonist imiquimod, and biomacromolecules such as CpG oligodeoxynucleot...

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Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling

Cited by 220 publications

References 35 publications

The updated landscape of tumor microenvironment and drug repurposing

The updated landscape of tumor microenvironment and drug repurposing

Unexpected guests in the tumor microenvironment: microbiome in cancer

Nanoscale Metal–Organic Frameworks for Cancer Immunotherapy

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