scholarly journals Identification of Cell Surface Molecules That Determine the Macrophage Activation Threshold Associated With an Early Stage of Malignant Transformation

2021 ◽  
Vol 12 ◽  
Author(s):  
Camille Jacqueline ◽  
Matthew Dracz ◽  
Sarah Boothman ◽  
Jonathan S. Minden ◽  
Rachel A. Gottschalk ◽  
...  
Keyword(s):  
Immune System ◽  
Malignant Transformation ◽  
Macrophage Activation ◽  
Early Stage ◽  
Successful Outcome ◽  
Activation Threshold ◽  
Surface Molecules ◽  
Cytokine Activation ◽  
Malignant Changes ◽  
Cancer Immunosurveillance

The ability of immune cells to sense changes associated with malignant transformation as early as possible is likely to be important for the successful outcome of cancer immunosurveillance. In this process, the immune system faces a trade-off between elimination of cells harboring premalignant or malignant changes, and autoimmune pathologies. We hypothesized that the immune system has therefore evolved a threshold for the stage of transformation from normal to fully malignant cells that first provides a threat (danger) signal requiring a response. We co-cultured human macrophages with a unique set of genetically related human cell lines that recapitulate successive stages in breast cancer development: MCF10A (immortalized, normal); MCFNeoT (benign hyperplasia); MCFT1 (atypical hyperplasia); MCFCA1 (invasive cancer). Using cytokines-based assays, we found that macrophages were inert towards MCF10A and MCFNeoT but were strongly activated by MCFT1 and MCFCA1 to produce inflammatory cytokines, placing the threshold for recognition between two premalignant stages, the earlier stage MCFNeoT and the more advanced MCFT1. The cytokine activation threshold paralleled the threshold for enhanced phagocytosis. Using proteomic and transcriptomic approaches, we identified surface molecules, some of which are well-known tumor-associated antigens, that were absent or expressed at low levels in MCF10A and MCFNeoT but turned on or over-expressed in MCFT1 and MCFCA1. Adding antibodies specific for two of these molecules, Annexin-A1 and CEACAM1, inhibited macrophage activation, supporting their role as cancer “danger signals” recognized by macrophages.

Novel Coronavirus SARS-CoV-2 (COVID-19) and Pregnancy: A hypothetical view

2020 ◽  
Vol 20 ◽  
Author(s):  
Ahmed RG
Keyword(s):  
Immune System ◽  
Cellular Therapy ◽  
Early Stage ◽  
Control Strategies ◽  
Vital Role ◽  
Healthy Life ◽  
Global Pandemic ◽  
Maternal Immune System ◽  
Perinatal Management ◽  
Novel Coronavirus

Background: The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. Objective: The aim of this review was to determine the transmission, severity, complications of SARS-CoV-2 infection during the pregnancy. This review showed the influence of COVID-19 disease on the neonatal neurogenesis. Owing to no specific vaccines or medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. Discussion: This overview showed in severely states that SARS-CoV-2 infection during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. Conclusion: During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international and national corporations should be continuing for perinatal management, particularly during the next pandemic or disaster time.

scholarly journals Immune System Efficiency in Cancer and the Microbiota Influence

Pathobiology ◽  
2021 ◽  
pp. 1-17
Author(s):  
Ana Margarida Barbosa ◽  
Alexandra Gomes-Gonçalves ◽  
António G. Castro ◽  
Egídio Torrado
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Checkpoint Inhibitors ◽  
Therapeutic Response ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Antitumor Immune Response ◽  
System Efficiency ◽  
Novel Targets ◽  
Cancer Immunosurveillance

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.

scholarly journals Immunoregulatory Property of C-Type Lectin-Like Receptors in Fibrosing Interstitial Lung Diseases

2020 ◽  
Vol 21 (10) ◽  
pp. 3665
Author(s):  
Wiwin Is Effendi ◽  
Tatsuya Nagano ◽  
Helmia Hasan ◽  
Resti Yudhawati
Keyword(s):  
Immune System ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Lung Diseases ◽  
Wound Repair ◽  
Tissue Injury ◽  
Interstitial Lung Diseases ◽  
Downstream Signaling ◽  
Cytokine Activation ◽  
Immune Impairment

The innate immune system identifies exogenous threats or endogenous stress through germline-encoded receptors called pattern recognition receptors (PRRs) that initiate consecutive downstream signaling pathways to control immune responses. However, the contribution of the immune system and inflammation to fibrosing interstitial lung diseases (ILD) remains poorly understood. Immunoreceptor tyrosine-based motif-bearing C-type lectin-like receptors (CTLRs) may interact with various immune cells during tissue injury and wound repair processes. Dectin-1 is a CTLR with dominant mechanisms manifested through its intracellular signaling cascades, which regulate fibrosis-promoting properties through gene transcription and cytokine activation. Additionally, immune impairment in ILD facilitates microbiome colonization; hence, Dectin-1 is the master protector in host pulmonary defense against fungal invasion. Recent progress in determining the signaling pathways that control the balance of fibrosis has implicated immunoreceptor tyrosine-based motif-bearing CTLRs as being involved, either directly or indirectly, in the pathogenesis of fibrosing ILD.

scholarly journals Receptors That Inhibit Macrophage Activation: Mechanisms and Signals of Regulation and Tolerance

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Ranferi Ocaña-Guzman ◽  
Luis Vázquez-Bolaños ◽  
Isabel Sada-Ovalle
Keyword(s):  
Immune System ◽  
Cell Lines ◽  
Immune Tolerance ◽  
Defense Mechanisms ◽  
Macrophage Activation ◽  
Immunological Tolerance ◽  
Innate Defense ◽  
Activation Mechanisms ◽  
Monocytes And Macrophages ◽  
Inhibitory Molecules

A variety of receptors perform the function of attenuating or inhibiting activation of cells in which they are expressed. Examples of these kinds of receptors include TIM-3 and PD-1, among others that have been widely studied in cells of lymphoid origin and, though to a lesser degree, in other cell lines. Today, several studies describe the function of these molecules as part of the diverse mechanisms of immune tolerance that exist in the immune system. This review analyzes the function of some of these proteins in monocytes and macrophages and as well as their participation as inhibitory molecules or elements of immunological tolerance that also act in innate defense mechanisms. We chose the receptors TIM-3, PD-1, CD32b, and CD200R because these molecules have distinct functional characteristics that provide examples of the different regulating mechanisms in monocytes and macrophages.

scholarly journals Borderline Ovarian Tumors: Fifteen Years’ Experience at a Scottish Tertiary Cancer Center

2018 ◽  
Vol 28 (9) ◽  
pp. 1683-1691 ◽  
Author(s):  
James May ◽  
Karolina Skorupskaite ◽  
Mario Congiu ◽  
Nidal Ghaoui ◽  
Graeme A. Walker ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Surgical Management ◽  
Early Stage ◽  
Ovarian Tumors ◽  
Ca 125 ◽  
Ovarian Malignancy ◽  
Borderline Ovarian Tumors ◽  
Gynecology And Obstetrics ◽  
Preoperative Serum

ObjectivesSince the recognition of borderline ovarian tumors (BOTs) in the 1970s, the management of this subset of epithelial ovarian tumors has presented a challenge to clinicians. The majority present at an early stage, but their diagnosis is often only made following surgery, hence the heterogeneity of surgical management. Borderline ovarian tumors are morphologically diverse, and their behavior is subsequently also heterogeneous. We aimed to assess recurrence rates and the rate of malignant transformation in patients diagnosed with BOT. Secondary objectives included a review of current management and assessment of tumor markers, stage, cyst dimensions, and the presence of micropapillary features as prognostic indicators of recurrence.MethodsThis retrospective cohort study included all patients treated with BOT between 2000 and 2015 in the southeast region of Scotland. Clinical, surgicopathological, and follow-up data were collated. Data were analyzed with reference to recurrence and malignant transformation.ResultsTwo hundred seventy-five patients underwent treatment for BOT in the study period. Surgical management was highly variable. A diagnosis of recurrent/persistent BOT or ovarian malignancy following initial treatment of BOT was rare, with only 12 (4%) of 275 cases. There were 7 cases (3%) of ovarian malignancy. Advanced International Federation of Gynecology and Obstetrics stage was the most prominent prognostic factor. Elevated preoperative serum CA-125 and the presence of micropapillary features correlated with advanced stage at presentation. With a lack of clear guidance, follow-up was highly variable with a median of 43 months (0–136 months).ConclusionsTo our knowledge, this study is the largest BOT cohort in the United Kingdom. Recurrent disease is rare in optimally staged, completely resected, early-stage BOT, without high-risk features. Caution is needed in women electing not to undergo completion staging after diagnosis and in those opting for a fertility-preserving approach. Thorough informed consent and clear plans for surveillance and follow-up are needed with consideration of delayed completion surgery as appropriate.

Human MUC1 Mucin: A Multifaceted Glycoprotein

2000 ◽  
Vol 15 (4) ◽  
pp. 343-356 ◽  
Author(s):  
S. von Mensdorff-Pouilly ◽  
F.G.M. Snijdewint ◽  
A.A. Verstraeten ◽  
R.H.M. Verheijen ◽  
P. Kenemans
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Early Stage ◽  
Immune Recognition ◽  
Breast Cancer Patients ◽  
Phase I Clinical Trials ◽  
Muc1 Mucin ◽  
Human Muc1

Human MUC1 mucin, a membrane-bound glycoprotein, is a major component of the ductal cell surface of normal glandular cells. MUC1 is overexpressed and aberrantly glycosylated in carcinoma cells. The role MUC1 plays in cancer progression represents two sides of one coin: on the one hand, loss of polarity and overexpression of MUC1 in cancer cells interferes with cell adhesion and shields the tumor cell from immune recognition by the cellular arm of the immune system, thus favoring metastases; on the other hand, MUC1, in essence a self-antigen, is displaced and altered in malignancy and induces immune responses. Tumor-associated MUC1 has short carbohydrate sidechains and exposed epitopes on its peptide core; it gains access to the circulation and comes into contact with the immune system provoking humoral and cellular immune responses. Natural antibodies to MUC1 present in the circulation of cancer patients may be beneficial to the patient by restricting tumor growth and dissemination: early stage breast cancer patients with a humoral response to MUC1 have a better disease-specific survival. Several MUC1 peptide vaccines, differing in vectors, carrier proteins and adjuvants, have been tested in phase I clinical trials. They are capable of inducing predominantly humoral responses to the antigen, but evidence that these immune responses may be effective against the tumor in humans is still scarce.

Identification of Target Antigens Recognized in MGUS for Immunotherapeutic Approaches.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3463-3463
Author(s):  
Simona Blotta ◽  
Roberto Bellucci ◽  
Pierfrancesco Tassone ◽  
Rao Prabhala ◽  
Paola Neri ◽  
...  
Keyword(s):  
Immune System ◽  
Antibody Response ◽  
Rna Binding ◽  
Early Stage ◽  
Disease Process ◽  
Complete Response ◽  
Donor Lymphocyte Infusion ◽  
Cdna Expression Library ◽  
Expression Library ◽  
Benign Condition

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with 30% of patient developing symptomatic multiple myeloma (MM). The events leading to the transformation from MGUS to MM remain unclear, however several evidences have supported the idea that the immune system, in patients with MGUS, may play a role in controlling the progression to MM; and the identification of antigenic targets could open the way for future immunotherapeutic approaches to delay or prevent such progression. To identify target antigens that are recognized by the immune system in MGUS, we have screened a cDNA expression library, produced from purified CD138+ bone marrow myeloma cells, with high dilution (1:500) serum from 3 MGUS patients with stable disease for 1 to 4 years. Using this approach we were able to identify a panel of 11 gene products to which an antibody response was observed in serum from individuals with MGUS. Responses appeared to be directed against intracellular proteins involved in variety of cellular functions such as apoptosis (SON, Hip1), DNA and RNA binding (KIAA0530, GPATC4), signal transduction regulators (AKAP11), transcriptional co-repressors (IRF2BP2), developmental proteins (OFD1) and proteins involved in the ubiquitin-proteosome pathway (PSMC1). Interestingly PSMC1, the 26S subunit of proteosome, has recently emerged as a potential target for antimyeloma therapies and AKAP11 located on the 13q14.11, a locus frequently involved in the pathogenesis of aggressive MM. Importantly, two of these identified genes with antibody response have been previously identified by SEREX screenings; KIAA0530 has been reported to induce a strong antibody response in solid tumors such as head and neck, testicular, breast and colorectal cancers and SON, a protein involved in apoptosis with similarities to oncoproteins such as myc and mos, has been previously reported by us to induce an antibody response associated with a complete response after donor lymphocyte infusion in patients with MM. Our studies are now focused on testing these proteins in a series of MGUS serum at different stages of disease as well as in early stage myeloma. Although preliminary, these data open the possibility to identify target antigens that are important in the disease process of MGUS and may allow us to design future vaccines and immunotherapeutic approaches targeting these antigens in MGUS as well as in MM.

Gene expression patterns in melanocytic cells: candidate markers for early stage and malignant transformation

2001 ◽  
Vol 196 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Clifton B. Meije ◽  
Theodorus B. M. Hakvoort ◽  
Guido W. M. Swart ◽  
Wiete Westerhof ◽  
Wouter H. Lamers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malignant Transformation ◽  
Early Stage ◽  
Expression Patterns ◽  
Gene Expression Patterns

FROM THE MODELING OF THE IMMUNE HALLMARKS OF CANCER TO A BLACK SWAN IN BIOLOGY

2013 ◽  
Vol 23 (05) ◽  
pp. 949-978 ◽  
Author(s):  
ABDELGHANI BELLOUQUID ◽  
ELENA DE ANGELIS ◽  
DAMIAN KNOPOFF
Keyword(s):  
Immune System ◽  
Kinetic Theory ◽  
Biological Function ◽  
Early Stage ◽  
Black Swan ◽  
Mathematical Approach ◽  
Hallmarks Of Cancer ◽  
Active Particles ◽  
Scalar Variable ◽  
Large Systems

This paper deals with the modeling of the early stage of cancer phenomena, namely mutations, onset, progression of cancer cells, and their competition with the immune system. The mathematical approach is based on the kinetic theory of active particles developed to describe the dynamics of large systems of interacting cells, called active particles. Their microscopic state is modeled by a scalar variable which expresses the main biological function. The modeling focuses on an interpretation of the immune-hallmarks of cancer.

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