IL-1β inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization

Castaño, Zafira; Juan, Beatriz P. San; Spiegel, Asaf; Pant, Ayush; DeCristo, Molly J.; Laszewski, Tyler; Ubellacker, Jessalyn M.; Janssen, Susanne R; Dongre, Anushka; Reinhardt, Ferenc; Henderson, Ayana; Río, Ana García del; Gifford, Ann; Herbert, Zachary T.; Hutchinson, John N.; Weinberg, Robert A.; Chaffer, Christine L.; McAllister, Sandra S.

doi:10.1038/s41556-018-0173-5

Cited by 136 publications

(94 citation statements)

References 71 publications

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“…B cells played the imperative role in the TME from various tumor samples, particularly in the ccRCC, with a mean of 4% across samples 4 cells had been established as a metastasis-promoter in bladder cancer 9 while opposite effects were also reported showing B cells could suppress other types of tumor development 32 . In the present study, we used in vitro migration assays, invasion assays, 3D invasion assays and in vivo tail vein injected mouse model to show that TEB cells could promote RCC metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidences showed that IL-1β level was increased in a variety of human tumors 35 . Specifically, Sandra McAllister reported that IL-1β inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization 32 . Regulatory B cells (Bregs), an important B cell subset producing IL-10, had been shown to contribute to autoimmune diseases, cancers, and chronic infections, which provided a possible mechanism how B cells turned into a tumor-promoter 36 .…”

Section: Discussionmentioning

confidence: 99%

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Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

Huang

et al. 2020

Cell Death Dis

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While B cells in the tumor microenvironment (TME) might play important roles in cancer progression, their impacts on the renal cell carcinoma (RCC) metastasis remained unclear, which drew our attention to further explore. We found that RCC tissues could recruit more B cells than the surrounding normal renal tissues from human clinical RCC samples. Wound healing assay, transwell assay and 3D invasion assays demonstrated that recruited B cells, also known as tumor-educated B cells (TEB), could significantly increase the RCC cell migration and invasion. In addition, in vivo data from xenograft RCC mouse model also confirmed that TEB could enhance RCC cell invasive and metastatic capability. Mechanism dissection revealed that TEB activated IL-1β/HIF-2α signals in RCC cells that could induce the downstream Notch1 signaling pathway. The above results demonstrated the key roles of TEB within renal cancer associated tumor microenvironment were metastasis-promotor and might help us to develop the potential therapies via targeting these newly identified IL-1β/HIF-2α/Notch1 signals in RCC progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

Huang

et al. 2020

Cell Death Dis

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“…At primary sites, IL-1 has been shown to promote tumor growth 7,29 . However, at secondary sites, studies suggest both prometastatic and antimetastatic roles for IL-1 signaling in models of breast cancer 30,31 . The divergent IL-1 responses in metastasis may be explained by different breast cancer subtypes.…”

Section: Discussionmentioning

confidence: 99%

Metastasis-initiating cells induce and exploit a fibroblast niche to fuel malignant colonization of the lungs

et al. 2020

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Metastatic colonization relies on interactions between disseminated cancer cells and the microenvironment in secondary organs. Here, we show that disseminated breast cancer cells evoke phenotypic changes in lung fibroblasts, forming a supportive metastatic niche. Colonization of the lungs confers an inflammatory phenotype in metastasis-associated fibroblasts. Specifically, IL-1α and IL-1β secreted by breast cancer cells induce CXCL9 and CXCL10 production in lung fibroblasts via NF-κB signaling, fueling the growth of lung metastases. Notably, we find that the chemokine receptor CXCR3, that binds CXCL9/10, is specifically expressed in a small subset of breast cancer cells, which exhibits tumor-initiating ability when co-transplanted with fibroblasts and has high JNK signaling that drives IL-1α/β expression. Importantly, disruption of the intercellular JNK-IL-1-CXCL9/10-CXCR3 axis reduces metastatic colonization in xenograft and syngeneic mouse models. These data mechanistically demonstrate an essential role for the molecular crosstalk between breast cancer cells and their fibroblast niche in the progression of metastasis.

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“…34 IL-1 signaling has also been associated with increased chemoresistance in mouse models of cancer 35 and production of protumorigenic IL-22. 36 In prognostic studies, higher tumor IL-1β levels have been associated with improved survival of patients with lymph node-positive breast cancer, 37 while the use of a blocking anti-IL-1β antibody in patients with cardiovascular diseases showed a reduction on lung cancer incidence. 38 Extracellular ATP activates NLRP3 inflammasome through P2×7 receptors.…”

Section: Introductionmentioning

confidence: 99%

On the mechanism of anti-CD39 immune checkpoint therapy

Allard

Stagg

2020

J Immunother Cancer

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With the coming of age of cancer immunotherapy, the search for new therapeutic targets has led to the identification of immunosuppressive adenosine as an important regulator of antitumor immunity. This resulted in the development of selective inhibitors targeting various components of the adenosinergic pathway, including small molecules antagonists targeting the high affinity A2A adenosine receptor and low affinity A2B receptor, therapeutic monoclonal antibodies (mAbs) and small molecules targeting CD73 and therapeutic mAbs targeting CD39. As each regulator of the adenosinergic pathway present non-overlapping biologic functions, a better understanding of the mechanisms of action of each targeted approach should accelerate clinical translation and improve rational design of combination treatments. In this review, we discuss the potential mechanisms-of-action of anti-CD39 cancer therapy and potential toxicities that may emerge from sustained CD39 inhibition. Caution should be taken, however, in extrapolating data from gene-targeted mice to patients treated with blocking anti-CD39 agents. As phase I clinical trials are now underway, further insights into the mechanism of action and potential adverse events associated with anti-CD39 therapy are anticipated in coming years.

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IL-1β inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization

Cited by 136 publications

References 71 publications

Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

Metastasis-initiating cells induce and exploit a fibroblast niche to fuel malignant colonization of the lungs

On the mechanism of anti-CD39 immune checkpoint therapy

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