scholarly journals Stromal Cells Present in the Melanoma Niche Affect Tumor Invasiveness and Its Resistance to Therapy

2021 ◽  
Vol 22 (2) ◽  
pp. 529
Author(s):  
Justyna Mazurkiewicz ◽  
Aleksandra Simiczyjew ◽  
Ewelina Dratkiewicz ◽  
Marcin Ziętek ◽  
Rafał Matkowski ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Current Knowledge ◽  
Response To Treatment ◽  
Pigment Cells ◽  
Factors Affecting ◽  
Tumor Invasiveness ◽  
Rapid Acquisition ◽  
Complex Interactions ◽  
Therapy Effectiveness

Malignant melanoma is a highly metastatic type of cancer, which arises frequently from transformed pigment cells and melanocytes as a result of long-term UV radiation exposure. In recent years, the incidence of newly diagnosed melanoma patients reached 5% of all cancer cases. Despite the development of novel targeted therapies directed against melanoma-specific markers, patients’ response to treatment is often weak or short-term due to a rapid acquisition of drug resistance. Among the factors affecting therapy effectiveness, elements of the tumor microenvironment play a major role. Melanoma niche encompasses adjacent cells, such as keratinocytes, cancer-associated fibroblasts (CAFs), adipocytes, and immune cells, as well as components of the extracellular matrix and tumor-specific physicochemical properties. In this review, we summarize the current knowledge concerning the influence of cancer-associated cells (keratinocytes, CAFs, adipocytes) on the process of melanomagenesis, tumor progression, invasiveness, and the emergence of drug resistance in melanoma. We also address how melanoma can alter the differentiation and activation status of cells present in the tumor microenvironment. Understanding these complex interactions between malignant and cancer-associated cells could improve the development of effective antitumor therapeutic strategies.

scholarly journals Regulation of Immunity in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1080 ◽  
Author(s):  
Chidalu Edechi ◽  
Nnamdi Ikeogu ◽  
Jude Uzonna ◽  
Yvonne Myal
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Economic Burden ◽  
Current Knowledge ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Breast Tumorigenesis ◽  
Complex Interactions

Breast cancer affects millions of women worldwide, leading to many deaths and significant economic burden. Although there are numerous treatment options available, the huge potentials of immunotherapy in the management of localized and metastatic breast cancer is currently being explored. However, there are significant gaps in understanding the complex interactions between the immune system and breast cancer. The immune system can be pro-tumorigenic and anti-tumorigenic depending on the cells involved and the conditions of the tumor microenvironment. In this review, we discuss current knowledge of breast cancer, including treatment options. We also give a brief overview of the immune system and comprehensively highlight the roles of different cells of the immune system in breast tumorigenesis, including recent research discoveries. Lastly, we discuss some immunotherapeutic strategies for the management of breast cancer.

ROS-responsive nanomedicine: Towards targeting the breast tumor microenvironment

2020 ◽  
Vol 28 ◽  
Author(s):  
RamaRao Malla ◽  
Mohammad Amjad Kamal
Keyword(s):  
Reactive Oxygen Species ◽  
Gene Therapy ◽  
Drug Resistance ◽  
Molecular Imaging ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Breast Tumor ◽  
Imaging Techniques ◽  
Oxygen Species ◽  
Massive Accumulation

: The breast tumor microenvironment (TME) promotes drug resistance through an elaborated interaction of TME components mediated by reactive oxygen species (ROS). Despite a massive accumulation of data concerning the targeting the ROS, but little is known about the ROS-responsive nanomedicine for targeting breast TME. This review submits the ROS landscape in breast TME, including ROS biology, ROS mediated carcinogenesis, reprogramming of stromal and immune cells of TME. We also discussed ROS-based precision strategies for imaging TME, including molecular imaging techniques with advanced probes, multiplexed methods, and multi-omic profiling strategies. ROS-responsive nanomedicine also describes various therapies, such as chemo-dynamic, photodynamic, photothermal, sono-dynamic, immune, and gene therapy for BC. We expound ROS-responsive primary delivery systems for chemotherapeutics, phytochemicals, and immunotherapeutics. This review also presents recent updates on nano-theranostics for simultaneous diagnosis and treatment of BCs. We assume that review on this advancing field will be beneficial to the development of ROS-based nanotheranostics for BC.

Targeting the Tumor Microenvironment by Intervention in Interleukin-1 Biology

2017 ◽  
Vol 23 (32) ◽  
pp. 4893-4905 ◽  
Author(s):  
Elena Voronov ◽  
Ron N. Apte
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Tumor Immunity ◽  
Biological Activities ◽  
Interleukin 1 ◽  
Tumor Development ◽  
Tumor Treatment ◽  
Tumor Invasiveness ◽  
First Line Therapy ◽  
Inflammatory Component

The importance of anti-tumor immunity in the outcome of cancer is now unequivocally established and recent achivements in the field have stimulated the development of new immunotherapeutical approaches. In invasive tumors, widespread inflammation promotes invasiveness and concomitantly also inhibits anti-tumor immune responses. We suggest that efficient tumor treatment should target both the malignant cells and the tumor microenvironment. Interleukin-1 (IL-1) is a pro-inflammatory as well as an immunostimulatory cytokine that is abundant in the tumor microenvironment. Manipulation of IL-1 can thus serve as an immunotherapeutical approach to reduce inflammation/immunosuppression and thus enhance anti-tumor immunity. The two major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to the same IL-1 signaling receptor and induce the same array of biological activities. The IL-1 receptor antagonist (IL-Ra) is a physiological inhibitor of IL-1 that binds to its receptor without transmition of activation signals and thus serves as a decoy target. We have demonstrated that IL-1α and IL-1β are different in terms of the producing cells and their compartmentalization and the amount. IL-1α is mainly expressed intracellularly, in the cytosol, in the nucleus or exposed on the cell membrane, however, it is rarely secreted. IL-1β is active only as a secreted molecule that is mainly produced by activated myeloid cells. We have shown different functions of IL-1α and IL-1β in the malignant process. Thus, in its membrane- associated form, IL-1α is mainly immunostimulatory, while IL-1β that is secreted into the tumor microenvironment is mainly pro-inflammatory and promotes tumorigenesis, tumor invasiveness and immunosuppression. These distinct functions of the IL-1 agonistic molecules are mainly manifested in early stages of tumor development and the patterns of their expression dictate the direction of the malignant process. Here, we suggest that IL-1 modulation can serve as an effective mean to tilt the balance between inflammation and immunity in tumor sites, towards the latter. Different agents that neutralize IL-1, mainly the IL-Ra and specific antibodies, exist. They are safe and FDA-approved. The IL-1Ra has been widely and successfully used in patients with Rheumatoid arthritis, autoinflammatory diseases and various other diseases that have an inflammatory component. Here, we provide the rationale and experimental evidence for the use of anti-IL-1 agents in cancer patients, following first line therapy to debulk the major tumor's mass. The considerations and constraints of using anti-IL-1 treatments in cancer are also discussed. We hope that this review will stimulate studies that will fasten the application of IL-1 neutralization at the bedside of cancer patients.

Predictive Factors Affecting the Success of Nephrectomy for the Treatment of Nephrogenic Hypertension: Multicenter Study

2021 ◽  
pp. 1-6
Author(s):  
Ediz Vuruskan ◽  
Hakan Ercil ◽  
Umut Unal ◽  
Ergun Alma ◽  
Hakan Anil ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Partial Response ◽  
Medical Treatment ◽  
Predictive Factors ◽  
Treatment Success ◽  
Complete Response ◽  
Response To Treatment ◽  
Factors Affecting ◽  
Success Of Treatment ◽  
Functioning Kidney

<b><i>Introduction:</i></b> The aim of our study is to evaluate the predictive factors affecting the success of treatment with nephrectomy in patients with poorly functioning kidney and nephrogenic hypertension. <b><i>Methods:</i></b> Data for patients who underwent nephrectomy with a diagnosis of nephrogenic hypertension in 3 centers between May 2010 and January 2020 were analyzed. In the postoperative period, if the blood pressure (BP) was below 140/90 mm Hg without medical treatment, it was accepted as complete response; if the arterial BP was below 140/90 mm Hg with medical treatment or less medication, it was accepted as partial response; and if BP did not decrease to normal values, it was accepted as unresponsive. Demographic characteristics, duration of hypertension, preoperative and postoperative BP values, and presence of metabolic syndrome were statistically evaluated. <b><i>Results:</i></b> Our study consisted of 91 patients with a mean preoperative hypertension duration of 23.3 ± 12.1 months. Among patients, 42 (46.2%) had complete response, 18 (19.8%) had partial response, and 31 (34.0%) had no response. Preoperative systolic and diastolic BP values were not effective on treatment success (<i>p</i> = 0.071, <i>p</i> = 0.973, respectively), but the increase in age and hypertension duration (<i>p</i> = 0.030 and <i>p</i> &#x3c; 0.001, respectively) and the presence of metabolic syndrome (<i>p</i> = 0.002) significantly decreased the complete response rates. <b><i>Conclusions:</i></b> Preoperative hypertension duration, advanced age, and presence of metabolic syndrome are predictive factors affecting the response to treatment in patients who undergo nephrectomy due to nephrogenic hypertension.

scholarly journals Hampering Stromal Cells in the Tumor Microenvironment as a Therapeutic Strategy to Destem Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3191
Author(s):  
Katherine Po Sin Chung ◽  
Rainbow Wing Hei Leung ◽  
Terence Kin Wah Lee
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Current Knowledge ◽  
Special Focus ◽  
Intrinsic Regulation ◽  
Mechanistic Basis ◽  
Novel Therapeutic Strategies

Cancer stem cells (CSCs) within the tumor bulk play crucial roles in tumor initiation, recurrence and therapeutic resistance. In addition to intrinsic regulation, a growing body of evidence suggests that the phenotypes of CSCs are also regulated extrinsically by stromal cells in the tumor microenvironment (TME). Here, we discuss the current knowledge of the interplay between stromal cells and cancer cells with a special focus on how stromal cells drive the stemness of cancer cells and immune evasive mechanisms of CSCs. Knowledge gained from the interaction between CSCs and stromal cells will provide a mechanistic basis for the development of novel therapeutic strategies for the treatment of cancers.

scholarly journals Interactions between Cancer-Associated Fibroblasts and T Cells in the Pancreatic Tumor Microenvironment and the Role of Chemokines

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2995
Author(s):  
Laia Gorchs ◽  
Helen Kaipe
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Current Knowledge ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
Cell Trafficking ◽  
Cancer Associated Fibroblasts ◽  
Cell Axis ◽  
Combinational Treatment

Less than 10% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) survive 5 years or more, making it one of the most fatal cancers. Accumulation of T cells in pancreatic tumors is associated with better prognosis, but immunotherapies to enhance the anti-tumor activity of infiltrating T cells are failing in this devastating disease. Pancreatic tumors are characterized by a desmoplastic stroma, which mainly consists of activated cancer-associated fibroblasts (CAFs). Pancreatic CAFs have emerged as important regulators of the tumor microenvironment by contributing to immune evasion through the release of chemokines, cytokines, and growth factors, which alters T-cell migration, differentiation and cytotoxic activity. However, recent discoveries have also revealed that subsets of CAFs with diverse functions can either restrain or promote tumor progression. Here, we discuss our current knowledge about the interactions between CAFs and T cells in PDAC and summarize different therapy strategies targeting the CAF–T cell axis with focus on CAF-derived soluble immunosuppressive factors and chemokines. Identifying the functions of different CAF subsets and understanding their roles in T-cell trafficking within the tumor may be fundamental for the development of an effective combinational treatment for PDAC.

Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains

2020 ◽  
Vol 75 (6) ◽  
pp. 1567-1574
Author(s):  
Daniela Sánchez ◽  
Solange Arazi Caillaud ◽  
Ines Zapiola ◽  
Silvina Fernandez Giuliano ◽  
Rosa Bologna ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Current Knowledge ◽  
Phylogenetic Analyses ◽  
Genotypic Diversity ◽  
Resistance Testing ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Middle Income ◽  
Subtype B ◽  
Hiv 1

Abstract Background Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate. Materials and methods HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses. Results Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%), 7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping. INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs. Conclusions Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the use of INIs.

scholarly journals CXCL12 and Its Isoforms: Different Roles in Pancreatic Cancer?

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Alessandra Righetti ◽  
Matteo Giulietti ◽  
Berina Šabanović ◽  
Giulia Occhipinti ◽  
Giovanni Principato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Invasion ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Tumor Development ◽  
Physiological Role ◽  
Mesenchymal Transition ◽  
Splicing Isoforms

CXCL12 is a chemokine that acts through CXCR4 and ACKR3 receptors and plays a physiological role in embryogenesis and haematopoiesis. It has an important role also in tumor development, since it is released by stromal cells of tumor microenvironment and alters the behavior of cancer cells. Many studies investigated the roles of CXCL12 in order to understand if it has an anti- or protumor role. In particular, it seems to promote tumor invasion, proliferation, angiogenesis, epithelial to mesenchymal transition (EMT), and metastasis in pancreatic cancer. Nevertheless, some evidence shows opposite functions; therefore research on CXCL12 is still ongoing. These discrepancies could be due to the presence of at least six CXCL12 splicing isoforms, each with different roles. Interestingly, three out of six variants have the highest levels of expression in the pancreas. Here, we report the current knowledge about the functions of this chemokine and then focus on pancreatic cancer. Moreover, we discuss the methods applied in recent studies in order to understand if they took into account the existence of the CXCL12 isoforms.

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