scholarly journals A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Isabel Carvalho ◽  
Ricardo Silva-Carvalho ◽  
Isabel Pires ◽  
Justina Prada ◽  
Rodolfo Bianchini ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Mammary Cancer ◽  
Inflammatory Cells ◽  
Mammary Carcinogenesis ◽  
Signaling Molecules ◽  
Comparative Approach ◽  
Human Breast ◽  
Infiltrating Cells ◽  
Inflammatory State

Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them. Cancer related inflammation has an important role in mammary carcinogenesis, contributing to the acquisition of core hallmark capabilities that allow cancer cells to survive, proliferate, and disseminate. Indeed, recent studies in human breast cancer and in canine mammary tumors have identified a growing list of signaling molecules released by inflammatory cells that serve as effectors of their tumor-promoting actions. These include the COX-2, the tumor EGF, the angiogenic VEGF, other proangiogenic factors, and a large variety of chemokines and cytokines that amplify the inflammatory state. This review describes the intertwined signaling pathways shared by T-lymphocytic/macrophage infiltrates and important tissue biomarkers in both human and dog mammary carcinogenesis.

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.

The role of atypical chemokine receptor-1 in breast cancer immune response.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23072-e23072 ◽  
Author(s):  
Rachel Martini ◽  
Petros Nikolinakos ◽  
Jamie Hodgson ◽  
Brittany Jenkins ◽  
Melissa Davis
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Chemokine Receptor ◽  
Immune Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Breast Tumors ◽  
Human Breast ◽  
Inflammatory Chemokines

e23072 Background: Interactions between chemokines and their receptors can regulate anti-tumor response by influencing the migration of immune cells. Atypical Chemokine Receptor 1 (ACKR1/DARC), a genetically diverse transmembrane GPCR, acts as a decoy receptor for a variety of CXC and CC chemokines, including those with pro-malignant and pro-inflammatory effects, such as CCL2 and CXCL8 . The purpose of this study is to determine if the migration of tumor-associated immune cells is unique based on epithelial ACKR1 expression on breast cancer cells, and if this association is correlated to an increase in pro-malignant chemokines, survival, or race. Methods: Immunohistochemistry techniques were used to determine expression of ACKR1 on primary breast tumors, along with T-cells, B-cells, dendritic cells, and macrophages. Concentrations of pro-inflammatory chemokines in circulation were determined using a Luminex-based immunoassay. In silco analyses were performed to determine associations between ACKR1 tumor status, race, and survival. Finally, using human breast cancer cell lines and immunofluorescence techniques, co-localization between ACKR1 and pro-inflammatory chemokines was investigated. Results: Results from these tests indicate that there is differential infiltration of immune cell types in tumors expressing ACKR1, , which were not detected in ACKR1 negative tumors. Significantly increased circulating CCL2 and CXCL8 chemokine levels we also determined to be positively correlated with ACKR1 expression in primary breast tumors. Survival analyses showed a significantly increased relapse free survival in patients having tumors with high ACKR1 expression, while investigations into racial differences revealed a significant race effect, with Caucasians having higher ACKR1 levels on their tumors than African-Americans. Finally, co-localization between ACKR1 with CCL2 and CXCL8 is observed in cultured human breast cancer cells. Conclusions: tumors positively expressing ACKR1 to have a more favorable prognosis suggest that a role of ACKR1 on breast tumor cells is to sequester pro-inflammatory chemokines in the tumor microenvironment, recruiting a distinct subset of tumor-associated immune cells.

Hyperprolactinaemia as an adverse effect in regulatory and clinical toxicology: role in breast and prostate cancer

2006 ◽  
Vol 25 (7) ◽  
pp. 395-404 ◽  
Author(s):  
P W Harvey ◽  
D J Everett ◽  
C J Springall
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Adverse Effect ◽  
Risk Factor ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Mammary Carcinogenesis ◽  
Prolactin Secretion ◽  
Human Breast ◽  
Breast And Prostate Cancer

Historically, hyperprolactinaemia has been considered of low toxicological relevance when detected in toxicity studies, and even mammary carcinogenesis induced in the rat by prolactin excess has been considered of no relevance to humans. However, recent findings from human epidemiology and molecular biology suggests that prolactin is a risk factor for human breast cancer, and probably prostate cancer. Therefore, this new evidence should be considered in the various decisions to develop and license a new drug or chemical if the compound causes hyperprolactinaemia. This emerging evidence suggests that prolactin can also be produced locally from human breast cancer cells, and that, regardless of source (ie, pituitary or autocrine/paracrine production from cancer cells), prolactin is mitogenic, stimulates proliferation and suppresses apoptosis in breast and prostate cancer cells. This review outlines the evidence that hyperprolactinaemia should be considered a toxicological adverse effect and concludes that prolactin-induced rodent mammary carcinogenesis is relevant to humans and is not species-specific. The effects of prolactin on the prostate gland are also discussed; hyperprolactinaemia may be an additional risk factor for prostate cancer and this also requires consideration in toxicological risk assessments. The implications of increased prolactin secretion as an adverse effect for regulatory toxicology of drugs and chemicals, and in high risk patients receiving therapeutic drugs with hyperprolactinaemic side effects, is discussed. Alteration of prolactin level is also a novel mechanism that requires consideration in endocrine disruption research, since both endogenous oestrogens and also xenoestrogens stimulate prolactin secretion or affect prolactin receptors.

The pulse vaccination effects in mammary carcinoma

2017 ◽  
Vol 10 (03) ◽  
pp. 1750036
Author(s):  
Chahinez Aboura ◽  
Tarik Mohamed Touaoula ◽  
Mourad Aribi
Keyword(s):  
Immune Responses ◽  
Cancer Cells ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Mammary Carcinogenesis ◽  
Pulse Vaccination ◽  
Total Cancer ◽  
Time Required ◽  
The Relationship ◽  
Theoretical Results

Induction of antitumor immunity by vaccination is one of the major current immunotherapy strategies. We present a mathematical model of the competition between immune cells and mammary carcinogenesis under the effect of Triplex vaccine. The model describes both humoral and cell-mediated immune responses against cancer cells. The control of the cancer cells growth occurs through the application of the pulse vaccination. Here we determine the relationship between the strength of the vaccine and the time required to eradicate cancer cells, and we present some simulations to illustrate our theoretical results, namely, the total cancer cells depletion, which is influenced by competition occurs among the immune and cancer cells.

scholarly journals Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Boutheina Cherif ◽  
Hana Triki ◽  
Slim Charfi ◽  
Lobna Bouzidi ◽  
Wala Ben Kridis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Human Breast Cancer ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Fine Tuning ◽  
Human Breast ◽  
Inflammatory Microenvironment

AbstractB7-H6 and PD-L1 belong to the B7 family co-stimulatory molecules fine-tuning the immune response. The present work investigates the clinical effect of B7-H6 protein expression with PD-L1 status and the infiltration of natural killer cells as potential biomarkers in breast tumor inflammatory microenvironment. The expression levels of B7-H6 protein by cancer cells and immune infiltrating cells in human breast cancer tissues and evaluate their associations with PD-L1 expression, NK cell status, clinical pathological features and prognosis were explored. The immunohistochemistry labeling method was used to assess B7-H6 and PD-L1 proteins expression by cancer and immune cells. The associations between immune checkpoint, major clinical pathological variables and survival rates were analyzed. B7-H6 protein was depicted in both breast and immune cells. Results showed that Tumor B7-H6 expression is highly associated with Her-2 over expression. B7-H6 + immune cells are highly related to the Scarff–Bloom–Richardson grade and associated with PD-L1 expression and NK cells status. Survival analysis revealed a better prognosis in patients with low expression of B7-H6 by cancer cells. Conversely, B7-H6 + immune cells were significantly associated with longer survival. Findings strongly suggest an interaction between B7 molecules that contributes to a particular design of the inflammatory microenvironment. This may influence the efficiency of therapies based on antibodies blocking the PD-L1/PD1 pathway and can explain the detection of clinical benefits only in a fraction of patients treated with immune checkpoint inhibitors.

scholarly journals Immune and Inflammatory Cells in Thyroid Cancer Microenvironment

2019 ◽  
Vol 20 (18) ◽  
pp. 4413 ◽  
Author(s):  
Ferrari ◽  
Fallahi ◽  
Galdiero ◽  
Ruffilli ◽  
Elia ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune System ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Checkpoint Inhibitors ◽  
Diagnostic Procedures ◽  
Inflammatory Cells ◽  
Cytotoxic Lymphocytes ◽  
Cytokines And Chemokines

A hallmark of cancer is the ability of tumor cells to avoid immune destruction. Activated immune cells in tumor microenvironment (TME) secrete proinflammatory cytokines and chemokines which foster the proliferation of tumor cells. Specific antigens expressed by cancer cells are recognized by the main actors of immune response that are involved in their elimination (immunosurveillance). By the recruitment of immunosuppressive cells, decreasing the tumor immunogenicity, or through other immunosuppressive mechanisms, tumors can impair the host immune cells within the TME and escape their surveillance. Within the TME, cells of the innate (e.g., macrophages, mast cells, neutrophils) and the adaptive (e.g., lymphocytes) immune responses are interconnected with epithelial cancer cells, fibroblasts, and endothelial cells via cytokines, chemokines, and adipocytokines. The molecular pattern of cytokines and chemokines has a key role and could explain the involvement of the immune system in tumor initiation and progression. Thyroid cancer-related inflammation is an important target for diagnostic procedures and novel therapeutic strategies. Anticancer immunotherapy, especially immune checkpoint inhibitors, unleashes the immune system and activates cytotoxic lymphocytes to kill cancer cells. A better knowledge of the molecular and immunological characteristics of TME will allow novel and more effective immunotherapeutic strategies in advanced thyroid cancer.

scholarly journals Immune Checkpoint Molecules B7-H6 and PD-L1 Co-Pattern The Tumor Inflammatory Microenvironment: Associations and Clinical Significance in Human Breast Cancer

2020 ◽  
Author(s):  
Boutheina Cherif ◽  
Hana Triki ◽  
Slim Charfi ◽  
Lobna Bouzidi ◽  
Wala Ben Kridis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Human Breast Cancer ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Fine Tuning ◽  
Human Breast ◽  
Inflammatory Microenvironment

Abstract B7-H6 and PD-L1 belong to the B7 family co-stimulatory molecules fine-tuning the immune response. This report exposes for the first time the clinical implication of B7-H6 protein expression in relation with PD-L1 status and Natural Killer Cells infiltration as potential biomarkers in tumor inflammatory microenvironment. Herein, we explore the expression levels of B7-H6 protein by cancer cells and immune infiltrating cells in human breast cancer tissues and evaluate their associations with PD-L1 expression, NK cell status and clinical pathological features as well as the prognosis. Immunohistochemistry labeling method was used to assess B7-H6 and PD-L1 proteins expression by cancer and immune cells. Associations between immune checkpoint, major clinicopathological variables and survival rates were analyzed. B7-H6 protein was revealed in both breast and immune cells. Tumor B7-H6 expression is highly associated with Her2 over expression. B7-H6 + immune cells are highly related to SBR grade and associated with PD-L1 and NK cells status. Survival analysis showed that patients with low expression of B7-H6 by cancer cells had better prognosis. Conversely, B7-H6 + immune cells were significantly associated with longer survival. Our result strongly suggests an interaction between B7 molecules that contributes to a particular design of the inflammatory microenvironment. This may influence the efficiency of therapies based on antibodies blocking the PD-L1/PD1 pathway and can explain why the clinical benefits are seen only in a fraction of patients treated with immune checkpoint inhibitors.

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