scholarly journals Crucial biological functions of CCL7 in cancer

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4928 ◽  
Author(s):  
Yangyang Liu ◽  
Yadi Cai ◽  
Li Liu ◽  
Yudong Wu ◽  
Xiangyang Xiong
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Suppressor ◽  
Immune Cells ◽  
Tumor Invasion ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Biological Functions ◽  
Invasion And Metastasis ◽  
Multiple Cell ◽  
Available Information

Chemokine (C-C motif) ligand 7 (CCL7), a CC chemokine, is a chemotactic factor and attractant for various kinds of leukocytes, including monocytes and neutrophils. CCL7 is widely expressed in multiple cell types and can participate in anti-inflammatory responses through binding to its receptors to mediate the recruitment of immune cells. Abnormal CCL7 expression is associated with certain immune diseases. Furthermore, CCL7 plays a pivotal role in tumorigenesis. CCL7 promotes tumor progression by supporting the formation of the tumor microenvironment and facilitating tumor invasion and metastasis, although some studies have suggested that CCL7 has tumor suppressor effects. In this review, we summarize the currently available information regarding the influence of CCL7 on tumors.

scholarly journals Clofarabine commandeers the RNR-α—ZRANB3 nuclear signaling axis

2019 ◽  
Author(s):  
Marcus J. C. Long ◽  
Yi Zhao ◽  
Yimon Aye
Keyword(s):  
Dna Synthesis ◽  
Tumor Invasion ◽  
Early Time ◽  
Cell Types ◽  
Drug Induced ◽  
Nuclear Signaling ◽  
Signaling Axis ◽  
Multiple Cell ◽  
Essential Enzyme ◽  
Approved Drugs

SummaryRibonucleotide reductase (RNR) is an essential enzyme in DNA-biogenesis and a target of several chemotherapeutics. Here we investigate how anti-leukemic drugs [e.g., clofarabine (ClF)] that target one of the two subunits of RNR, RNR-α, affect non-canonical RNR-α functions. We discovered that these clinically-approved RNR-inhibiting dATP-analogs inhibit growth by also targeting ZRANB3—a newly-identified DNA-synthesis promoter and nuclear-localized interactor of RNR-α. Remarkably, in early time points following drug treatment, ZRANB3-targeting accounted for most of the drug-induced DNA-synthesis suppression and multiple cell types featuring ZRANB3-knockout/knockdown were resistant to these drugs. Additionally, ZRANB3 plays a major role in regulating tumor-invasion and H-rasG12V-promoted transformation in a manner dependent on the recently-discovered interactome of RNR-α involving select cytosolic-/nuclear-localized protein-players. The H-rasG12V-promoted transformation—which we show requires ZRANB3-supported DNA-synthesis—was efficiently suppressed by ClF. Such overlooked mechanisms-of-action of approved drugs and a new example of non-oncogene addiction, which is suppressed by RNR-α, may advance cancer interventions.

scholarly journals The Tumor Microenvironment of Epithelial Ovarian Cancer and Its Influence on Response to Immunotherapy

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 242 ◽  
Author(s):  
Galaxia Rodriguez ◽  
Kristianne Galpin ◽  
Curtis McCloskey ◽  
Barbara Vanderhyden
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
B Lymphocytes ◽  
Immune Cells ◽  
Ovarian Cancer Cell ◽  
Cell Types ◽  
Therapeutic Approaches ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Immunotherapy as a treatment for cancer is a growing field of endeavor but reports of success have been limited for epithelial ovarian cancer. Overcoming the challenges to developing more effective therapeutic approaches lies in a better understanding of the factors in cancer cells and the surrounding tumor microenvironment that limit response to immunotherapies. This article provides an overview of some ovarian cancer cell features such as tumor-associated antigens, ovarian cancer-derived exosomes, tumor mutational burden and overexpression of immunoinhibitory molecules. Moreover, we describe relevant cell types found in epithelial ovarian tumors including immune cells (T and B lymphocytes, Tregs, NK cells, TAMs, MDSCs) and other components found in the tumor microenvironment including fibroblasts and the adipocytes in the omentum. We focus on how those components may influence responses to standard treatments or immunotherapies.

scholarly journals Applications of Single-Cell Omics to Dissect Tumor Microenvironment

2020 ◽  
Vol 11 ◽  
Author(s):  
Tingting Guo ◽  
Weimin Li ◽  
Xuyu Cai
Keyword(s):  
Tumor Microenvironment ◽  
Single Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Immune Checkpoint Blockade ◽  
Lineage Tracing ◽  
Great Success ◽  
Novel Technologies ◽  
Single Cell Sequencing

The recent technical and computational advances in single-cell sequencing technologies have significantly broaden our toolkit to study tumor microenvironment (TME) directly from human specimens. The TME is the complex and dynamic ecosystem composed of multiple cell types, including tumor cells, immune cells, stromal cells, endothelial cells, and other non-cellular components such as the extracellular matrix and secreted signaling molecules. The great success on immune checkpoint blockade therapy has highlighted the importance of TME on anti-tumor immunity and has made it a prime target for further immunotherapy strategies. Applications of single-cell transcriptomics on studying TME has yielded unprecedented resolution of the cellular and molecular complexity of the TME, accelerating our understanding of the heterogeneity, plasticity, and complex cross-interaction between different cell types within the TME. In this review, we discuss the recent advances by single-cell sequencing on understanding the diversity of TME and its functional impact on tumor progression and immunotherapy response driven by single-cell sequencing. We primarily focus on the major immune cell types infiltrated in the human TME, including T cells, dendritic cells, and macrophages. We further discuss the limitations of the existing methodologies and the prospects on future studies utilizing single-cell multi-omics technologies. Since immune cells undergo continuous activation and differentiation within the TME in response to various environmental cues, we highlight the importance of integrating multimodal datasets to enable retrospective lineage tracing and epigenetic profiling of the tumor infiltrating immune cells. These novel technologies enable better characterization of the developmental lineages and differentiation states that are critical for the understanding of the underlying mechanisms driving the functional diversity of immune cells within the TME. We envision that with the continued accumulation of single-cell omics datasets, single-cell sequencing will become an indispensable aspect of the immune-oncology experimental toolkit. It will continue to drive the scientific innovations in precision immunotherapy and will be ultimately adopted by routine clinical practice in the foreseeable future.

scholarly journals Tumor-Infiltrating Immune Cells Promoting Tumor Invasion and Metastasis: Existing Theories

2013 ◽  
Vol 4 (1) ◽  
pp. 84-95 ◽  
Author(s):  
Yan-gao Man ◽  
Alexander Stojadinovic ◽  
Jeffrey Mason ◽  
Itzhak Avital ◽  
Anton Bilchik ◽  
...  
Keyword(s):  
Immune Cells ◽  
Tumor Invasion ◽  
Invasion And Metastasis

scholarly journals Theranostic Probes for Targeting Tumor Microenvironment: An Overview

2017 ◽  
Author(s):  
Musafar Gani Sikkandhar ◽  
Anu Maashaa Nedumaran ◽  
Roopa Ravichandar ◽  
Satnam Singh ◽  
Induja Santhakumar ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Nuclear Imaging ◽  
Future Perspective ◽  
Resonance Imaging ◽  
Invasion And Metastasis ◽  
Connective Tissues ◽  
Anticancer Drug Delivery ◽  
Promote Tumor Growth ◽  
Magnetic Resonance Imaging Mri

Long gone was the time when tumors were thought to be insular masses of cells, residing independently at specific sites in an organ. Now, researchers gradually realize that tumors interact with the extracellular matrix (ECM), blood vessels, connective tissues and immune cells in their environment, which is now known as the tumor microenvironment (TME). It is found that the interactions between tumors and their surrounding promote tumor growth, invasion and metastasis. The dynamics and diversity of TME cause the tumors to be heterogeneous and thus pose a challenge for cancer diagnosis, drug design and therapy. As TME is significant in enhancing tumor progression, it is vital to identify the different components in the TME. This review explores how different factors in the TME supply tumors with the required growth factors and signaling molecules to proliferate, invade and metastasis. We also examine the development of TME-targeted nanotheranostics over the recent years for cancer therapy, diagnosis and anticancer drug delivery system. This review further discusses the limitations and future perspective of nanoparticle based theranostics when used in combination with current imaging modalities like Optical Imaging, Magnetic Resonance Imaging (MRI) and Nuclear Imaging (PET and SPECT).

scholarly journals Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 137
Author(s):  
Zhi-Jian Han ◽  
Yang-Bing Li ◽  
Lu-Xi Yang ◽  
Hui-Juan Cheng ◽  
Xin Liu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Immune Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Checkpoint Inhibitors ◽  
Lymphatic Vessels ◽  
Cell Types ◽  
Mesenchymal Transition ◽  
Development Of Resistance ◽  
Immunosuppressive Cells

In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of CXCL8 on individual cell types can result in cascading alterations to the TME. The changes in the TME components such as the cancer-associated fibroblasts (CAFs), the immune cells, the extracellular matrix, the blood vessels, or the lymphatic vessels further influence tumor progression and therapeutic resistance. Emerging roles of the microbiome in tumorigenesis or tumor progression revealed the intricate interactions between inflammatory response, dysbiosis, metabolites, CXCL8, immune cells, and the TME. Studies have shown that CXCL8 directly contributes to TME remodeling, cancer plasticity, and the development of resistance to both chemotherapy and immunotherapy. Further, clinical data demonstrate that CXCL8 could be an easily measurable prognostic biomarker in patients receiving immune checkpoint inhibitors. The blockade of the CXCL8-CXCR1/2 axis alone or in combination with other immunotherapy will be a promising strategy to improve antitumor efficacy. Herein, we review recent advances focusing on identifying the mechanisms between TME components and the CXCL8-CXCR1/2 axis for novel immunotherapy strategies.

SARS-CoV-2 Biology Insights, Part III. The COVID-19 latency hypotheses and the fertility question. (Preprint)

2020 ◽  
Author(s):  
Laura Lafon-Hughes ◽  
Deborah J Keszenman
Keyword(s):  
Literature Review ◽  
Immune Cells ◽  
Persistent Infection ◽  
Latent Infection ◽  
Rna Virus ◽  
Cell Types ◽  
Latent Infections ◽  
Maternal Transmission ◽  
Multiple Cell ◽  
Do So

BACKGROUND As already reviewed in Part I, SARS-CoV-2 Spike is optimized for infection of multiple cell types, including immune cells. Accordingly, as reviewed in Part II, it can generate a systemic persistent infection. OBJECTIVE Now, two questions are addressed. First, whether it can be discarded that SARS-CoV-2 might remain as a latent infection to be reactivated by a stress years later. Second, whether it can or not be transmitted to descendants. METHODS A literature review was done through Google searches in order to know, first, if ss(+)RNA virus can establish latent infections. Then, regarding partially known mechanisms to do so. Third, wondering whether SARS-CoV-2 has the necessary elements to establish a latent infection using mechanisms similar to the ones previously reported. Apart from that, it was also searched whether there were reports of SARS-CoV-2 in semen, maternal transmission or fertility issues. RESULTS An hypotheses regarding COVID-19 latency is raised. The question regarding fertility is unanswered. CONCLUSIONS There is plenty of work to be done. In the meantime, as will be discussed in Part V Viewpoint, it is a good idea to make an effort to stay uninfected if possible, particularly for the young generations.

Tumor microenvironment acid-sensitive liposomes enhanced colorectal cancer therapy by acting on both tumor cells and cancer-associated fibroblasts

Nanoscale ◽  
2021 ◽  
Author(s):  
chenglei li ◽  
Zhaohuan Li ◽  
Xue Gong ◽  
Jianhao Liu ◽  
Tingyue Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Crucial Role ◽  
Tumor Invasion ◽  
Cancer Associated Fibroblasts ◽  
Invasion And Metastasis ◽  
Promising Strategy

Cancer-associated fibroblasts (CAFs) play a crucial role in facilitating tumor invasion and metastasis, which act as the “soils” in tumor microenvironment (TME). Accordingly, it would be a promising strategy to...

scholarly journals Integrating Mendelian randomization and multiple-trait colocalization to uncover cell-specific inflammatory drivers of autoimmune and atopic disease

2019 ◽  
Vol 28 (19) ◽  
pp. 3293-3300 ◽  
Author(s):  
Lucy M McGowan ◽  
George Davey Smith ◽  
Tom R Gaunt ◽  
Tom G Richardson
Keyword(s):  
Gene Expression ◽  
Mendelian Randomization ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Atopic Disease ◽  
Analytical Framework ◽  
Causal Variant ◽  
Human Populations ◽  
Multiple Trait ◽  
Multiple Cell

Abstract Immune-mediated diseases (IMDs) arise when tolerance is lost and chronic inflammation is targeted towards healthy tissues. Despite their growing prevalence, therapies to treat IMDs are lacking. Cytokines and their receptors orchestrate inflammatory responses by regulating elaborate signalling networks across multiple cell types making it challenging to pinpoint therapeutically relevant drivers of IMDs. We developed an analytical framework that integrates Mendelian randomization (MR) and multiple-trait colocalization (moloc) analyses to highlight putative cell-specific drivers of IMDs. MR evaluated causal associations between the levels of 10 circulating cytokines and 9 IMDs within human populations. Subsequently, we undertook moloc analyses to assess whether IMD trait, cytokine protein and corresponding gene expression are driven by a shared causal variant. Moreover, we leveraged gene expression data from three separate cell types (monocytes, neutrophils and T cells) to discern whether associations may be attributed to cell type-specific drivers of disease. MR analyses supported a causal role for IL-18 in inflammatory bowel disease (IBD) (P = 1.17 × 10−4) and eczema/dermatitis (P = 2.81 × 10−3), as well as associations between IL-2rα and IL-6R with several other IMDs. Moloc strengthened evidence of a causal association for these results, as well as providing evidence of a monocyte and neutrophil-driven role for IL-18 in IBD pathogenesis. In contrast, IL-2rα and IL-6R associations were found to be T cell specific. Our analytical pipeline can help to elucidate putative molecular pathways in the pathogeneses of IMDs, which could be applied to other disease contexts.

Sign in / Sign up

Export Citation Format

Share Document