scholarly journals Strategies for Remodeling the Tumor Microenvironment Using Active Ingredients of Ginseng—A Promising Approach for Cancer Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Mo Li ◽  
Xin Wang ◽  
Ying Wang ◽  
Shunchao Bao ◽  
Qing Chang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Current Status ◽  
Active Ingredients ◽  
Active Components ◽  
Nano Drug Delivery ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Potential Applications ◽  
Tumor Research

The tumor microenvironment (TME) plays a key role in promoting the initiation and progression of tumors, leading to chemoradiotherapy resistance and immunotherapy failure. Targeting of the TME is a novel anti-tumor therapeutic approach and is currently a focus of anti-tumor research. Panax ginseng C. A. Meyer (ginseng), an ingredient of well-known traditional Asia medicines, exerts beneficial anti-tumor effects and can regulate the TME. Here, we present a systematic review that describes the current status of research efforts to elucidate the functions and mechanisms of ginseng active components (including ginsenosides and ginseng polysaccharides) for achieving TME regulation. Ginsenosides have variety effects on TME, such as Rg3, Rd and Rk3 can inhibit tumor angiogenesis; Rg3, Rh2 and M4 can regulate the function of immune cells; Rg3, Rd and Rg5 can restrain the stemness of cancer stem cells. Ginseng polysaccharides (such as red ginseng acidic polysaccharides and polysaccharides extracted from ginseng berry and ginseng leaves) can regulate TME mainly by stimulating immune cells. In addition, we propose a potential mechanistic link between ginseng-associated restoration of gut microbiota and the tumor immune microenvironment. Finally, we describe recent advances for improving ginseng efficacy, including the development of a nano-drug delivery system. Taken together, this review provides novel perspectives on potential applications for ginseng active ingredients as anti-cancer adjuvants that achieve anti-cancer effects by reshaping the tumor microenvironment.

scholarly journals The effect of PEGylation on the efficacy and uptake of an immunostimulatory nanoparticle in the tumor immune microenvironment

2021 ◽  
Author(s):  
Wyatt M. Becicka ◽  
Peter Bielecki ◽  
Morgan Lorkowski ◽  
Taylor J. Moon ◽  
Yahan Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Immunosuppressive Tumor Microenvironment

The efficacy of immunotherapies is often limited by the immunosuppressive tumor microenvironment, which is populated with dysfunctional innate immune cells. To reprogram the tumor-resident innate immune cells, we developed an...

Can Intratumoral neutrophil lymphocyte ratio (NLR) be a prognostic biomarker in breast cancer patients?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12573-e12573
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Vijayashree Murthy ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Immune Cells ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
High Group ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive

e12573 Background: In breast cancer patients, it is well known that the elevation of neutrophil lymphocyte ratio (NLR) in the blood are reported to associate with poor prognosis based on the notion that neutrophils represent pro-cancer, and lymphocytes represent anti-cancer immune cells. Tumor immune microenvironment has been demonstrated to play critical roles in the outcome of breast cancer patients. However, there is scarce evidence on the clinical relevance of intratumoral NLR in breast cancer patients. In the current study, we hypothesized that intratumoral NLR high tumors are associated with worse survival particularly in TNBC that is known to have high immune cell infiltration. Methods: A total of 1904 breast cancer patients’ data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) and analyzed. NLR was calculated by the gene expressions of CD66b (CEACAM8) and CD8 (CD8A). NLR high and low were divided by the median. Overall Survival (OS) and Disease-Free Survival were calculated utilizing Kaplan Meier method between intratumoral NLR high and low groups. xCell algorithm was used to analyze the infiltrated immune cells within the tumor immune microenvironment as we have previously published. Results: Intratumoral NLR high group was associated with worse OS in whole, ER-positive/HER2-negative, and triple negative (TN) subtypes, in agreement with the previous studies. TN subtype alone demonstrated worse DFS of NLR high group. Surprisingly, gene set enrichment analysis (GSEA) demonstrated no gene set enrichment to NLR high group, which implicates that there is no distinctive mechanism that associate with worse survival. Whereas, immune response-related gene sets significantly enriched to NLR low group in TN subtype. This enrichment was consistent in ER-positive/HER2-negative. Compared with ER-positive/HER2-negative subtype, anti-cancer immune cells such as CD4+ T cells, CD8+ T cells, M1 macrophage, and helper T helper type 1 cells were significantly infiltrated in TN patients (p < 0.001 for all genes), where M2 macrophages and neutrophils were less and regulatory T cells and T helper type 2 cells were more infiltrated in TN subtype. Furthermore, intratumoral NLR was significantly lower in TN compared with ER-positive/HER2-negative subtype (p < 0.001). These results suggest that intratumoral NLR low group is associated with better survival due to favorable tumor immune microenvironment in TN subtype rather than NLR high group has worse survival. Conclusions: Intratumoral NLR low tumor demonstrated more favorable OS and more favorable DFS in TN patients. Intratumoral NLR low breast cancer was associated with enhanced immune response and higher infiltration of anti-cancer immune cells were observed in TN subtype compared to ER-positive/HER2-negative which may contribute to the favorable outcome of in TN breast cancer.

scholarly journals Semaphorin Signaling in Cancer-Associated Inflammation

2019 ◽  
Vol 20 (2) ◽  
pp. 377 ◽  
Author(s):  
Giulia Franzolin ◽  
Luca Tamagnone
Keyword(s):  
Immune Response ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Disease Progression ◽  
Tumor Cells ◽  
Cross Talk ◽  
Immune Cells ◽  
Major Element ◽  
Inflammatory Cells ◽  
Anti Cancer

The inflammatory and immune response elicited by the growth of cancer cells is a major element conditioning the tumor microenvironment, impinging on disease progression and patients’ prognosis. Semaphorin receptors are widely expressed in inflammatory cells, and their ligands are provided by tumor cells, featuring an intense signaling cross-talk at local and systemic levels. Moreover, diverse semaphorins control both cells of the innate and the antigen-specific immunity. Notably, semaphorin signals acting as inhibitors of anti-cancer immune response are often dysregulated in human tumors, and may represent potential therapeutic targets. In this mini-review, we provide a survey of the best known semaphorin regulators of inflammatory and immune cells, and discuss their functional impact in the tumor microenvironment.

Clinical relevance of miR-143 expression in ER-positive breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12574-e12574
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
Manabu Futamura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Cells ◽  
High Expression ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive

e12574 Background: MicroRNA-143(miR-143) is a well-known tumor suppressive microRNA in various malignancies, including breast cancer. Recently, the tumor immune microenvironment has been reported to associate with progression of breast cancers. However, the association with the tumor immune microenvironment and miR-143 in breast cancers remains ambiguous. Given these backgrounds, we hypothesized that high expression of miR-143 is associated with favorable effect to the tumor immune microenvironment which leads to better survival of ER positive breast cancer patients. Methods: Two major publicly available breast cancer cohorts were used for this study. A total of 753 patients from The Cancer Genome Atlas (TCGA) and total of 1283 patients from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used. Results: We defined the higher quartile of miR-143 expression levels as high and the remainder as low expression groups. There was no significant difference in patient clinicopathlogical features between two groups. Gene set enrichment analysis (GSEA) revealed that miR-143 high expression tumors enriched Helper T cell type 1 (Th1) related gene sets indicating the upregulation of anti-cancer immune cells. Also, the cell composition of anti-cancer immune cells, such as Th1 and Macrophage M1 were higher with miR-143 high tumors (p < 0.001 and p < 0.01 respectively) in whole group. On the contrary, pro-cancer immune cells such as Th2 and M1 were lower with miR-143 high tumors (p < 0.01 and p < 0.001 respectively) in whole group. Interestingly, among the subtypes, we found that ER positive subgroup followed this trend of high infiltration rate of anti-cancer immune cells and low infiltration rate of pro-cancer immune cells. Furthermore, only ER positive subgroup demonstrated the survival benefit with miR-143 high expression tumors. Conclusions: We demonstrated that high expression of miR-143 in ER breast cancer associate with favorable tumor immune microenvironment, upregulation of the anti-cancer immune cells and suppression of the pro-cancer immune cells, and associate with better survival of the breast cancer patients.

scholarly journals A High Epigenetic Risk Score Shapes the Non-Inflamed Tumor Microenvironment in Breast Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Dong Zhang ◽  
Yingnan Wang ◽  
Qifeng Yang
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
High Risk ◽  
Tumor Microenvironment ◽  
Risk Score ◽  
Immune Cells ◽  
Immune Checkpoints ◽  
Cancer Immunity ◽  
Anti Cancer ◽  
Risk Patients

Background: Epigenetic dysregulation via aberrant DNA methylation has gradually become recognized as an efficacious signature for predicting tumor prognosis and response to therapeutic targets. However, reliable DNA methylation biomarkers describing tumorigenesis remain to be comprehensively explored regarding their prognostic and therapeutic potential in breast cancer (BC).Methods: Whole-genome methylation datasets integrated from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were profiled (n = 1,268). A three-stage selection procedure (discovery, training, and external validation) was utilized to screen out the prominent biomarkers and establish a robust risk score from more than 300,000 CpG sites after quality control, rigorous filtering, and reducing dimension. Moreover, gene set enrichment analyses guided us to systematically correlate this epigenetic risk score with immunological characteristics, including immunomodulators, anti-cancer immunity cycle, immune checkpoints, tumor-infiltrating immune cells and a series of signatures upon modulating components within BC tumor microenvironment (TME). Multi-omics data analyses were performed to decipher specific genomic alterations in low- and high-risk patients. Additionally, we also analyzed the role of risk score in predicting response to several treatment options.Results: A 10-CpG-based prognostic signature which could significantly and independently categorize BC patients into distinct prognoses was established and sufficiently validated. And we hypothesize that this signature designs a non-inflamed TME in BC based on the evidence that the derived risk score is negatively correlated with tumor-associated infiltrating immune cells, anti-cancer immunity cycle, immune checkpoints, immune cytolytic activity, T cell inflamed score, immunophenoscore, and the vast majority of immunomodulators. The identified high-risk patients were characterized by upregulation of immune inhibited oncogenic pathways, higher TP53 mutation and copy number burden, but lower response to cancer immunotherapy and chemotherapy.Conclusion: Our work highlights the complementary roles of 10-CpG-based signature in estimating overall survival in BC patients, shedding new light on investigating failed events concerning immunotherapy at present.

scholarly journals Iron Metabolism in the Tumor Microenvironment—Implications for Anti-Cancer Immune Response

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 303
Author(s):  
Alessandro Sacco ◽  
Anna Martina Battaglia ◽  
Cirino Botta ◽  
Ilenia Aversa ◽  
Serafina Mancuso ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Iron Metabolism ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Tumor Infiltrating Lymphocytes ◽  
Oxygen Species ◽  
Iron Availability ◽  
Anti Cancer ◽  
Immune Exclusion ◽  
Infiltrating Lymphocytes

New insights into the field of iron metabolism within the tumor microenvironment have been uncovered in recent years. Iron promotes the production of reactive oxygen species, which may either trigger ferroptosis cell death or contribute to malignant transformation. Once transformed, cancer cells divert tumor-infiltrating immune cells to satisfy their iron demand, thus affecting the tumor immunosurveillance. In this review, we highlight how the bioavailability of this metal shapes complex metabolic pathways within the tumor microenvironment and how this affects both tumor-associated macrophages and tumor-infiltrating lymphocytes functions. Furthermore, we discuss the potentials as well as the current clinical controversies surrounding the use of iron metabolism as a target for new anticancer treatments in two opposed conditions: (i) the “hot” tumors, which are usually enriched in immune cells infiltration and are extremely rich in iron availability within the microenvironment, and (ii) the “cold” tumors, which are often very poor in immune cells, mainly due to immune exclusion.

scholarly journals High Expression of microRNA-143 is Associated with Favorable Tumor Immune Microenvironment and Better Survival in Estrogen Receptor Positive Breast Cancer

2020 ◽  
Vol 21 (9) ◽  
pp. 3213 ◽  
Author(s):  
Yoshihisa Tokumaru ◽  
Mariko Asaoka ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Li Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Cells ◽  
High Expression ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive ◽  
Positive Breast Cancer

microRNA-143 (miR-143) is a well-known tumor suppressive microRNA that exhibits anti-tumoral function by targeting KRAS signaling pathways in various malignancies. We hypothesized that miR-143 suppresses breast cancer progression by targeting KRAS and its effector molecules. We further hypothesized that high expression of miR-143 is associated with a favorable tumor immune microenvironment of estrogen receptor (ER)-positive breast cancer patients which result in improved survival. Two major publicly available breast cancer cohorts; The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used. The miR-143 high expression group was associated with increased infiltration of anti-cancer immune cells and decreased pro-cancer immune cells, as well as enrichment of the genes relating to T helper (Th1) cells resulting in improved overall survival (OS) in ER-positive breast cancer patients. To the best of our knowledge, this is the first study to demonstrate that high expression of miR-143 in cancer cells associates with a favorable tumor immune microenvironment, upregulation of anti-cancer immune cells, and suppression of the pro-cancer immune cells, associating with better survival of the breast cancer patients.

scholarly journals Tuft and Cancer Stem Cell Marker DCLK1: A New Target to Enhance Anti-Tumor Immunity in the Tumor Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3801
Author(s):  
Zhiyun Cao ◽  
Nathaniel Weygant ◽  
Parthasarathy Chandrakesan ◽  
Courtney W. Houchen ◽  
Jun Peng ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Stem Cell Marker ◽  
Biological Processes ◽  
Cancer Stem Cell Marker ◽  
Immune Microenvironment ◽  
Mesenchymal Transition ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Small Molecular Inhibitors

Microtubule-associated doublecortin-like kinase 1 (DCLK1) is an accepted marker of tuft cells (TCs) and several kinds of cancer stem cells (CSCs), and emerging evidence suggests that DCLK1-positive TCs participate in the initiation and formation of inflammation-associated cancer. DCLK1-expressing CSCs regulate multiple biological processes in cancer, promote resistance to therapy, and are associated with metastasis. In solid tumor cancers, tumor epithelia, immune cells, cancer-associated fibroblasts, endothelial cells and blood vessels, extracellular matrix, and hypoxia all support a CSC phenotype characterized by drug resistance, recurrence, and metastasis. Recently, studies have shown that DCLK1-positive CSCs are associated with epithelial-mesenchymal transition, angiogenesis, and immune checkpoint. Emerging data concerning targeting DCLK1 with small molecular inhibitors, monoclonal antibodies, and chimeric antigen receptor T-cells shows promising effects on inhibiting tumor growth and regulating the tumor immune microenvironment. Overall, DCLK1 is reaching maturity as an anti-cancer target and therapies directed against it may have potential against CSCs directly, in remodeling the tumor microenvironment, and as immunotherapies.

scholarly journals Molecules and functions of aesculus chinensis bunge bark volatiles

2018 ◽  
pp. 809 ◽  
Author(s):  
Zuming Li
Keyword(s):  
Organic Solvent ◽  
Skin Care ◽  
Biologically Active ◽  
Active Ingredients ◽  
Active Components ◽  
Pyrolysis Products ◽  
Potential Applications ◽  
Main Components ◽  
Skin Care Products

This paper analyzes the organic solvent extracts of Aesculus chinensis Bunge Bark using TG and Py-GC-MS. The pyrolysis products were analyzed by GC-MS. The results showed that the extracts of Aesculus chinensis Bunge Bark contain a large number of biologically active components, including hydrocarbons, acids, ethers, alcohols, and phenols. The main components in the extract of Aesculus chinensis Bunge Bark are healthy and abundant; the main representatives of the active ingredients are Scopoletin Vanillin, Eugeno, Pyridine, p-Cresol, Indoles, Maltol and Furfural. There are potential applications in bioenergy, biopharmaceuticals, cosmetics, skin care products, and spices.

Regulation of tumor immune microenvironment by sphingolipids and lysophosphatidic acid

2021 ◽  
Vol 22 ◽  
Author(s):  
Supriya Vishwakarma ◽  
Neha Arya ◽  
Ashok Kumar
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Lysophosphatidic Acid ◽  
Immune Cells ◽  
Cancer Therapeutics ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Sphingosine 1 Phosphate ◽  
Patient Prognosis

: The tumor microenvironment (TME) consists of cancer cells that interact with stromal components such as the extracellular matrix, blood, and lymphatic networks, fibroblasts, adipocytes, and the cells of the immune system. Further, the tumor immune microenvironment, majorly represented by the tumor-infiltrating immune cells (TIIC), plays an important role in cancer therapeutics and patient prognosis. In fact, a high density of TIICs within the tumor microenvironment is known to be associated with better outcomes in several types of cancers. Towards this, two bioactive lipid molecules, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) regulate the homing of immune cells to the TME. In the present review, we will uncover the role of LPA and S1P signaling in the tumor immune environment, highlighting the latest progress in this field.

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