The tumor microenvironment and inflammatory breast cancer

Huang, Aji; Cao, Shousong; Tang, Lili

doi:10.7150/jca.17595

Cited by 52 publications

(38 citation statements)

References 42 publications

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“…Many studies have suggested that the activation of important inflammatory mediators such as NF-κB contributes to the aggressiveness and pathogenesis of IBC [ 19 , 20 , 21 , 22 , 23 ]. NF-κB is known to play a crucial role in tumor cell proliferation, differentiation, apoptosis, invasion, and metastasis [ 18 , 19 , 20 , 60 ]. RIPK2 is an upstream activator of NF-κB that is able to induce ubiquitination of NF-κB essential modulator.…”

Section: Discussionmentioning

confidence: 99%

RIPK2: New Elements in Modulating Inflammatory Breast Cancer Pathogenesis

Zare

Petrova

Agoumi

et al. 2018

Cancers

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Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that is associated with significantly high mortality. In spite of advances in IBC diagnoses, the prognosis is still poor compared to non-IBC. Due to the aggressive nature of the disease, we hypothesize that elevated levels of inflammatory mediators may drive tumorigenesis and metastasis in IBC patients. Utilizing IBC cell models and patient tumor samples, we can detect elevated NF-κB activity and hyperactivation of non-canonical drivers of NF-κB (nuclear factor kappaB)-directed inflammation such as tyrosine phosphorylated receptor-interacting protein kinase 2 (pY RIPK2), when compared to non-IBC cells or patients. Interestingly, elevated RIPK2 activity levels were present in a majority of pre-chemotherapy samples from IBC patients at the time of diagnosis to suggest that patients at diagnosis had molecular activation of NF-κB via RIPK2, a phenomenon we define as “molecular inflammation”. Surprisingly, chemotherapy did cause a significant increase in RIPK2 activity and thus molecular inflammation suggesting that chemotherapy does not resolve the molecular activation of NF-κB via RIPK2. This would impact on the metastatic potential of IBC cells. Indeed, we can demonstrate that RIPK2 activity correlated with advanced tumor, metastasis, and group stage as well as body mass index (BMI) to indicate that RIPK2 might be a useful prognostic marker for IBC and advanced stage breast cancer.

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Section: Discussionmentioning

confidence: 99%

RIPK2: New Elements in Modulating Inflammatory Breast Cancer Pathogenesis

Zare

Petrova

Agoumi

et al. 2018

Cancers

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“…Investigating tumor physiology through its micro-environmental biology is an attractive angle for treatment optimization. Understanding the micro-environmental imprint and its potential stereotypical response to classical anti-cancer strategies may help to define broader therapeutic combination options which could be less resistant ( 22 ) and consistent with the increasingly common paradigm of “personalizing medicine.” Indeed, some micro-environmental characteristics are rare within a subgroup of defined specific tumor patients but may be studied and better understood if present in other more frequent primary tumor subtypes. In this context, TLS have shown a common physiological pattern, which is independent from the primary tumor subtype/organs and may stimulate common strategies applicable to various cancers ( 10 , 23 ).…”

Section: Discussionmentioning

confidence: 99%

Cellular Composition and Contribution of Tertiary Lymphoid Structures to Tumor Immune Infiltration and Modulation by Radiation Therapy

et al. 2018

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Immune-based anti-cancer strategies combined with radiation therapy (RT) are actively being investigated but many questions remain, such as the ideal treatment scheme and whether a potent immune response can be generated both locally and systemically. In this context, tumor-associated tertiary lymphoid structures (TLS) have become a subject of research. While TLS are present in several types of cancer with strong similarities, they are especially relevant in medullary breast carcinoma (MBC). This suggests that MBC patients are ideally suited for investigating this question and may benefit from adapted therapeutic options. As RT is a corner-stone of MBC treatment, investigating interactions between RT and TLS composition is also clinically relevant. We thus first characterized the lymphoid structures associated with MBC in a patient case report and demonstrated that they closely resemble the TLS observed in a genetical mouse model. In this model, we quantitatively and qualitatively investigated the cellular composition of the tumor-associated TLS. Finally, we investigated TLS regulation after hypo-fractionated RT and showed that RT induced their acute and transient depletion, followed by a restoration phase. This study is the first work to bring a comprehensive and timely characterization of tumor-associated TLS in basal conditions and after RT. It highlights cellular targets (i.e., Tregs) that could be selectively modulated in subsequent studies to optimize anti-tumor immune response. The study of TLS modulation is worth further investigation in the context of RT and personalized medicine.

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“…Early diagnosis and effective treatment are the hope for cancer patients. Treatments include surgery, radiation, chemotherapy, hormone therapy, immune therapy, and targeted therapy . Although these treatments are generally good, they have some side‐effect in one way or another .…”

Section: Introductionmentioning

confidence: 99%

Nanosonosensitization by Using Copper–Cysteamine Nanoparticles Augmented Sonodynamic Cancer Treatment

Wang

et al. 2018

Part & Part Syst Charact

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Sonodynamic therapy (SDT), as a newly emerging and promising modality for cancer treatment, has been extensively investigated but with limited therapeutic outcome because of the absence of highly efficient sonosensitizer. Copper–cysteamine (Cu–Cy), as a new sensitizer, has been reported for oxidative therapy which can be activated with light, X‐ray, or microwave. Herein, for the first time, Cu–Cy nanoparticles are reported as new sonosensitizers for SDT on breast cancer treatment. Upon exposure of Cu–Cy nanoparticles to ultrasound, a large quantity of reactive oxygen species (ROS) are generated for cancer cell destruction with a high SDT efficiency to induce cell apoptosis and necrosis as observed in vitro. In vivo animal studies show a significant inhibition of tumor growth for the xenografts of 4T1 cancer cells with the combination of 0.75 mg kg−1 Cu–Cy and ultrasound. Overall, the preliminary results show that Cu–Cy nanoparticles can significantly augment the levels of ROS induced by ultrasound, demonstrating Cu–Cy is a new kind of efficient sonosensitzers for SDT applications. Such therapeutic platform by integrating a noninvasive, highly safe, deep‐penetration ultrasound modality. and quickly developed versatile nanosensitizers for tumor eradication will facilitate SDT future clinical translation.

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The tumor microenvironment and inflammatory breast cancer

Cited by 52 publications

References 42 publications

RIPK2: New Elements in Modulating Inflammatory Breast Cancer Pathogenesis

RIPK2: New Elements in Modulating Inflammatory Breast Cancer Pathogenesis

Cellular Composition and Contribution of Tertiary Lymphoid Structures to Tumor Immune Infiltration and Modulation by Radiation Therapy

Nanosonosensitization by Using Copper–Cysteamine Nanoparticles Augmented Sonodynamic Cancer Treatment

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