scholarly journals Cross Talk of Macrophages with Tumor Microenvironment Cells and Modulation of Macrophages in Cancer by Virotherapy

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1309
Author(s):  
Sarah Di Somma ◽  
Fabiana Napolitano ◽  
Giuseppe Portella ◽  
Anna Maria Malfitano
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Tumor Response ◽  
Cell Interaction ◽  
Oncolytic Viruses ◽  
Malignant Cells ◽  
Cellular Compartments ◽  
Stromal Stem Cells

Cellular compartments constituting the tumor microenvironment including immune cells, fibroblasts, endothelial cells, and mesenchymal stromal/stem cells communicate with malignant cells to orchestrate a series of signals that contribute to the evolution of the tumor microenvironment. In this study, we will focus on the interplay in tumor microenvironment between macrophages and mesenchymal stem cells and macrophages and fibroblasts. In particular, cell–cell interaction and mediators secreted by these cells will be examined to explain pro/anti-tumor phenotypes induced in macrophages. Nonetheless, in the context of virotherapy, the response of macrophages as a consequence of treatment with oncolytic viruses will be analyzed regarding their polarization status and their pro/anti-tumor response.

Mesenchymal Stem Cells and Cancer Stem Cells: An Overview of Tumor-Mesenchymal Stem Cell Interaction for therapeutic interventions

2021 ◽  
Vol 22 ◽  
Author(s):  
Soheila Montazersaheb ◽  
Ezzatollah Fathi ◽  
Ayoub Mamandi ◽  
Raheleh Farahzadi ◽  
Hamid Reza Heidari
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Cell Types ◽  
Cell Interaction ◽  
Therapeutic Interventions ◽  
Tumorigenic Potential ◽  
Different Types

: Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.

scholarly journals The Crosstalk between Ovarian Cancer Stem Cell Niche and the Tumor Microenvironment

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Manuel Varas-Godoy ◽  
Gregory Rice ◽  
Sebastián E. Illanes
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Stem Cell Niche ◽  
Small Population ◽  
The World ◽  
Cell Niche

Ovarian cancer is one of the most important causes of cancer-related death among women in the world. Despite advances in ovarian cancer treatment, 70–80% of women who initially respond to therapy eventually relapse and die. There is evidence that a small population of cells within the tumors called cancer stem cells (CSCs) could be responsible for treatment failure due to their enhanced chemoresistance and tumorigenicity. These cells reside in a niche that maintains the principal properties of CSCs. These properties are associated with the capacity of CSCs to interact with different cells of the tumor microenvironment including mesenchymal stem cells, endothelial cells, immune cells, and fibroblasts, promoting cancer progression. This interaction can be mediated by cytokines, growth factors, lipids, and/or extracellular vesicles released in the CSC niche. In this review, we will discuss how the interaction between ovarian CSCs and the tumor microenvironment can contribute to the maintenance of the CSC niche and consequently to tumor progression in ovarian cancer.

Mesenchymal Stem Cells, Immune Cells and Tumor Cells Crosstalk: A Sinister Triangle in the Tumor Microenvironment

2019 ◽  
Vol 14 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Mahboobeh Razmkhah ◽  
Shabnam Abtahi ◽  
Abbas Ghaderi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immune Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Mesenchymal Stem Cells [MSCs] are a heterogeneous population of fibroblast-like cells which maintain self-renewability and pluripotency. Many studies have demonstrated the immunomodulatory effects of MSCs on the innate and adaptive immune cells. As a result of interactions with tumor cells, microenvironment and immune-stimulating milieu, MSCs contribute to tumor progression by several mechanisms, including sustained proliferative signal in cancer stem cells [CSCs], inhibition of tumor cell apoptosis, transition to tumor-associated fibroblasts [TAFs], promotion of angiogenesis, stimulation of epithelial-mesenchymal transition [EMT], suppression of immune responses, and consequential promotion of tumor metastasis. Here, we present an overview of the latest findings on Janusfaced roles that MSCs play in the tumor microenvironment [TME], with a concise focus on innate and adaptive immune responses.

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Communication ◽  
Extra Cellular Matrix ◽  
Cytokine Signaling ◽  
Cellular Matrix

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001684
Author(s):  
Rafael Moreno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Oncolytic Viruses ◽  
Immunogenic Cell Death ◽  
The Past ◽  
Physical Barriers ◽  
Immunogenic Properties ◽  
New Strategies

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.

Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2–dependent regulatory dendritic cell population

Blood ◽  
2009 ◽  
Vol 113 (1) ◽  
pp. 46-57 ◽  
Author(s):  
Bin Zhang ◽  
Rui Liu ◽  
Dan Shi ◽  
Xingxia Liu ◽  
Yuan Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
Immune Cells ◽  
Cell Contact ◽  
Multilineage Differentiation ◽  
Immunomodulatory Effects ◽  
Cd11b Expression ◽  
Dendritic Cell Population

Abstract Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2–dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.

Characterization of patient-derived bone marrow human mesenchymal stem cells as oncolytic virus carriers for the treatment of glioblastoma

2021 ◽  
pp. 1-11
Author(s):  
Yuzaburo Shimizu ◽  
Joy Gumin ◽  
Feng Gao ◽  
Anwar Hossain ◽  
Elizabeth J. Shpall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Oncolytic Viruses ◽  
In Vivo Studies ◽  
Systemic Delivery ◽  
Previously Treated

OBJECTIVE Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical application. Bone marrow–derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigated as virus carriers. However, it is unclear whether BM-hMSCs can be derived from glioma patients previously treated with marrow-toxic chemotherapy or whether such BM-hMSCs can deliver oncolytic viruses effectively. Herein, the authors undertook a prospective clinical trial to determine the feasibility of obtaining BM-hMSCs from patients with recurrent malignant glioma who were previously exposed to marrow-toxic chemotherapy. METHODS The authors enrolled 5 consecutive patients who had been treated with radiation therapy and chemotherapy. BM aspirates were obtained from the iliac crest and were cultured to obtain BM-hMSCs. RESULTS The patient-derived BM-hMSCs (PD-BM-hMSCs) had a morphology similar to that of healthy donor–derived BM-hMSCs (HD-BM-hMSCs). Flow cytometry revealed that all 5 cell lines expressed canonical MSC surface markers. Importantly, these cultures could be made to differentiate into osteocytes, adipocytes, and chondrocytes. In all cases, the PD-BM-hMSCs homed to intracranial glioma xenografts in mice after intracarotid delivery as effectively as HD-BM-hMSCs. The PD-BM-hMSCs loaded with Delta-24-RGD (PD-BM-MSC-D24) effectively eradicated human gliomas in vitro. In in vivo studies, intravascular administration of PD-BM-MSC-D24 increased the survival of mice harboring U87MG gliomas. CONCLUSIONS The authors conclude that BM-hMSCs can be acquired from patients previously treated with marrow-toxic chemotherapy and that these PD-BM-hMSCs are effective carriers for oncolytic viruses.

scholarly journals Blood and Cancer: Cancer Stem Cells as Origin of Hematopoietic Cells in Solid Tumor Microenvironments

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1293 ◽  
Author(s):  
Ghmkin Hassan ◽  
Masaharu Seno
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cancer Cells ◽  
Solid Tumor ◽  
Immune Cells ◽  
Hematopoietic Cells ◽  
Hematopoietic Stem ◽  
Tumor Microenvironments

The concepts of hematopoiesis and the generation of blood and immune cells from hematopoietic stem cells are some steady concepts in the field of hematology. However, the knowledge of hematopoietic cells arising from solid tumor cancer stem cells is novel. In the solid tumor microenvironment, hematopoietic cells play pivotal roles in tumor growth and progression. Recent studies have reported that solid tumor cancer cells or cancer stem cells could differentiate into hematopoietic cells. Here, we discuss efforts and research that focused on the presence of hematopoietic cells in tumor microenvironments. We also discuss hematopoiesis from solid tumor cancer stem cells and clarify the notion of differentiation of solid tumor cancer stem cells into non-cancer hematopoietic stem cells.

scholarly journals The Role of Tumor-Associated Macrophages in Leukemia

2019 ◽  
Vol 143 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Yueyang Li ◽  
M. James You ◽  
Yaling Yang ◽  
Dongzhi Hu ◽  
Chen Tian
Keyword(s):  
Stem Cells ◽  
Innate Immunity ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Leukemia Cell ◽  
Tumor Associated Macrophages ◽  
Intrinsic Factors ◽  
Different Types ◽  
Tumor Growth And Metastasis

In addition to intrinsic factors, leukemia cell growth is influenced by the surrounding nonhematopoietic cells in the leukemic microenvironment, including fibroblasts, mesenchymal stem cells, vascular cells, and various immune cells. Despite the fact that macrophages are an important component of human innate immunity, tumor-associated macrophages (TAMs) have long been considered as an accomplice promoting tumor growth and metastasis. TAMs are activated by an abnormal malignant microenvironment, polarizing into a specific phenotype and participating in tumor progression. TAMs that exist in the microenvironment of different types of leukemia are called leukemia-associated macrophages (LAMs), which are reported to be associated with the progression of leukemia. This review describes the role of LAMs in different leukemia subtypes.

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