scholarly journals The Influence of Tumor Microenvironment on Immune Escape of Melanoma

2020 ◽  
Vol 21 (21) ◽  
pp. 8359 ◽  
Author(s):  
Aleksandra Simiczyjew ◽  
Ewelina Dratkiewicz ◽  
Justyna Mazurkiewicz ◽  
Marcin Ziętek ◽  
Rafał Matkowski ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Escape ◽  
Cell Types ◽  
Melanoma Cells ◽  
Cancer Therapies ◽  
System A ◽  
Anti Cancer ◽  
Low Efficiency ◽  
Inflammatory Molecules

The low efficiency of currently-used anti-cancer therapies poses a serious challenge, especially in the case of malignant melanoma, a cancer characterized by elevated invasiveness and relatively high mortality rate. The role of the tumor microenvironment in the progression of melanoma and its acquisition of resistance to treatment seems to be the main focus of recent studies. One of the factors that, in normal conditions, aids the organism in its fight against the cancer and, following the malignant transformation, adapts to facilitate the development of the tumor is the immune system. A variety of cell types, i.e., T and B lymphocytes, macrophages, and dendritic and natural killer cells, as well as neutrophils, support the growth and invasiveness of melanoma cells, utilizing a plethora of mechanisms, including secretion of pro-inflammatory molecules, induction of inhibitory receptors expression, or depletion of essential nutrients. This review provides a comprehensive summary of the processes regulated by tumor-associated cells that promote the immune escape of melanoma cells. The described mechanisms offer potential new targets for anti-cancer treatment and should be further studied to improve currently-employed therapies.

scholarly journals Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature

2021 ◽  
Vol 10 ◽  
Author(s):  
Aukie Hooglugt ◽  
Miesje M. van der Stoel ◽  
Reinier A. Boon ◽  
Stephan Huveneers
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Metastasis ◽  
Lymphatic Vessels ◽  
Cancer Therapies ◽  
Tumor Cell Growth ◽  
Vascular Normalization ◽  
Cancer Treatments ◽  
Anti Cancer ◽  
Tumor Endothelium

Solid tumors are dependent on vascularization for their growth. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, and permeable vasculature. The tumor vessels promote tumor metastasis and complicate delivery of anti-cancer therapies. In many types of tumors, YAP/TAZ activation is correlated with increased levels of angiogenesis. In addition, endothelial YAP/TAZ activation is important for the formation of new blood and lymphatic vessels during development. Oncogenic activation of YAP/TAZ in tumor cell growth and invasion has been studied in great detail, however the role of YAP/TAZ within the tumor endothelium remains insufficiently understood, which complicates therapeutic strategies aimed at targeting YAP/TAZ in cancer. Here, we overview the upstream signals from the tumor microenvironment that control endothelial YAP/TAZ activation and explore the role of their downstream targets in driving tumor angiogenesis. We further discuss the potential for anti-cancer treatments and vascular normalization strategies to improve tumor therapies.

The CXCL12/CXCR4/ACKR3 Axis in the Tumor Microenvironment: Signaling, Crosstalk, and Therapeutic Targeting

2021 ◽  
Vol 61 (1) ◽  
pp. 541-563 ◽  
Author(s):  
Martine J. Smit ◽  
Géraldine Schlecht-Louf ◽  
Maria Neves ◽  
Jelle van den Bor ◽  
Petronila Penela ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Chemokine Receptors ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cancer Therapies ◽  
Signaling Crosstalk ◽  
Wide Range ◽  
Elevated Expression

Elevated expression of the chemokine receptors CXCR4 and ACKR3 and of their cognate ligand CXCL12 is detected in a wide range of tumors and the tumor microenvironment (TME). Yet, the molecular mechanisms by which the CXCL12/CXCR4/ACKR3 axis contributes to the pathogenesis are complex and not fully understood. To dissect the role of this axis in cancer, we discuss its ability to impinge on canonical and less conventional signaling networks in different cancer cell types; its bidirectional crosstalk, notably with receptor tyrosine kinase (RTK) and other factors present in the TME; and the infiltration of immune cells that supporttumor progression. We discuss current and emerging avenues that target the CXCL12/CXCR4/ACKR3 axis. Coordinately targeting both RTKs and CXCR4/ACKR3 and/or CXCL12 is an attractive approach to consider in multitargeted cancer therapies. In addition, inhibiting infiltrating immune cells or reactivating the immune system along with modulating the CXCL12/CXCR4/ACKR3 axis in the TME has therapeutic promise.

scholarly journals Lipin-1, a Versatile Regulator of Lipid Homeostasis, Is a Potential Target for Fighting Cancer

2021 ◽  
Vol 22 (9) ◽  
pp. 4419
Author(s):  
Laura Brohée ◽  
Julie Crémer ◽  
Alain Colige ◽  
Christophe Deroanne
Keyword(s):  
Lipid Metabolism ◽  
Tumor Microenvironment ◽  
Adjuvant Therapy ◽  
Cancer Cells ◽  
Therapeutic Strategy ◽  
Lipid Homeostasis ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Lipin 1

The rewiring of lipid metabolism is a major adaptation observed in cancer, and it is generally associated with the increased aggressiveness of cancer cells. Targeting lipid metabolism is therefore an appealing therapeutic strategy, but it requires a better understanding of the specific roles played by the main enzymes involved in lipid biosynthesis. Lipin-1 is a central regulator of lipid homeostasis, acting either as an enzyme or as a co-regulator of transcription. In spite of its important functions it is only recently that several groups have highlighted its role in cancer. Here, we will review the most recent research describing the role of lipin-1 in tumor progression when expressed by cancer cells or cells of the tumor microenvironment. The interest of its inhibition as an adjuvant therapy to amplify the effects of anti-cancer therapies will be also illustrated.

Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

2020 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Milena Kostadinova ◽  
Milena Mourdjeva
Keyword(s):  
Cancer Cells ◽  
Small Population ◽  
Tumor Formation ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
New Methods ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

scholarly journals CCL2: An Important Mediator Between Tumor Cells and Host Cells in Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiakang Jin ◽  
Jinti Lin ◽  
Ankai Xu ◽  
Jianan Lou ◽  
Chao Qian ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cell Types ◽  
Host Cells ◽  
Specific Cell ◽  
Tumor Patients ◽  
Multiple Tumor ◽  
Inflammatory Monocytes ◽  
Immunosuppressive Cell ◽  
Tumor Types

Tumor microenvironment (TME) formation is a major cause of immunosuppression. The TME consists of a considerable number of macrophages and stromal cells that have been identified in multiple tumor types. CCL2 is the strongest chemoattractant involved in macrophage recruitment and a powerful initiator of inflammation. Evidence indicates that CCL2 can attract other host cells in the TME and direct their differentiation in cooperation with other cytokines. Overall, CCL2 has an unfavorable effect on prognosis in tumor patients because of the accumulation of immunosuppressive cell subtypes. However, there is also evidence demonstrating that CCL2 enhances the anti-tumor capability of specific cell types such as inflammatory monocytes and neutrophils. The inflammation state of the tumor seems to have a bi-lateral role in tumor progression. Here, we review works focusing on the interactions between cancer cells and host cells, and on the biological role of CCL2 in these processes.

scholarly journals The critical immunosuppressive effect of MDSC-derived exosomes in the tumor microenvironment

2020 ◽  
Author(s):  
Mohammad H. Rashid ◽  
Thaiz F. Borin ◽  
Roxan Ara ◽  
Raziye Piranlioglu ◽  
Bhagelu R. Achyut ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
Cell Types ◽  
Biological Macromolecules

AbstractMyeloid-derived suppressor cells (MDSCs) are an indispensable component of the tumor microenvironment (TME), and our perception regarding the role of MDSCs in tumor promotion is attaining extra layer of intricacy in every study. In conjunction with MDSC’s immunosuppressive and anti-tumor immunity, they candidly facilitate tumor growth, differentiation, and metastasis in several ways that yet to be explored. Alike any other cell types, MDSCs also release a tremendous amount of exosomes or nanovesicles of endosomal origin and partake in intercellular communications by dispatching biological macromolecules. There has not been any experimental study done to characterize the role of MDSCs derived exosomes (MDSC exo) in the modulation of TME. In this study, we isolated MDSC exo and demonstrated that they carry a significant amount of proteins that play an indispensable role in tumor growth, invasion, angiogenesis, and immunomodulation. We observed higher yield and more substantial immunosuppressive potential of exosomes isolated from MDSCs in the primary tumor area than those are in the spleen or bone marrow. Our in vitro data suggest that MDSC exo are capable of hyper activating or exhausting CD8 T-cells and induce reactive oxygen species production that elicits activation-induced cell death. We confirmed the depletion of CD8 T-cells in vivo by treating the mice with MDSC exo. We also observed a reduction in pro-inflammatory M1-macrophages in the spleen of those animals. Our results indicate that immunosuppressive and tumor-promoting functions of MDSC are also implemented by MDSC-derived exosomes which would open up a new avenue of MDSC research and MDSC-targeted therapy.

scholarly journals MicroRNAs and Apoptosis in Colorectal Cancer

2020 ◽  
Vol 21 (15) ◽  
pp. 5353 ◽  
Author(s):  
Hsiuying Wang
Keyword(s):  
Colorectal Cancer ◽  
Treatment Resistance ◽  
Therapeutic Resistance ◽  
Cancer Therapies ◽  
Malignant Cells ◽  
Apoptosis Induction ◽  
The Third ◽  
Anti Cancer ◽  
The World

Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is rising in developing countries. Treatment with 5-Fluorouracil (5-FU) is known to improve survival in CRC patients. Most anti-cancer therapies trigger apoptosis induction to eliminate malignant cells. However, de-regulated apoptotic signaling allows cancer cells to escape this signaling, leading to therapeutic resistance. Treatment resistance is a major challenge in the development of effective therapies. The microRNAs (miRNAs) play important roles in CRC treatment resistance and CRC progression and apoptosis. This review discusses the role of miRNAs in contributing to the promotion or inhibition of apoptosis in CRC and the role of miRNAs in modulating treatment resistance in CRC cells.

scholarly journals Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Xianjie Jiang ◽  
Jie Wang ◽  
Xiangying Deng ◽  
Fang Xiong ◽  
Junshang Ge ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Escape ◽  
Tumor Immune Escape

Multiscale homogenization for fluid and drug transport in vascularized malignant tissues

2014 ◽  
Vol 25 (01) ◽  
pp. 79-108 ◽  
Author(s):  
R. Penta ◽  
D. Ambrosi ◽  
A. Quarteroni
Keyword(s):  
Drug Transport ◽  
Reaction Model ◽  
Diffusion Reaction ◽  
Momentum Balance ◽  
Cancer Therapies ◽  
Multiscale Expansion ◽  
Anti Cancer ◽  
Intercapillary Distance ◽  
Multiscale Homogenization

A system of differential equations for coupled fluid and drug transport in vascularized (malignant) tissues is derived by a multiscale expansion. We start from mass and momentum balance equations, stated in the physical domain, geometrically characterized by the intercapillary distance (the microscale). The Kedem–Katchalsky equations are used to account for blood and drug exchange across the capillary walls. The multiscale technique (homogenization) is used to formulate continuum equations describing the coupling of fluid and drug transport on the tumor length scale (the macroscale), under the assumption of local periodicity; macroscale variations of the microstructure account for spatial heterogeneities of the angiogenic capillary network. A double porous medium model for the fluid dynamics in the tumor is obtained, where the drug dynamics is represented by a double advection–diffusion–reaction model. The homogenized equations are straightforward to approximate, as the role of the vascular geometry is recovered at an average level by solving standard cell differential problems. Fluid and drug fluxes now read as effective mass sources in the macroscale model, which upscale the interplay between blood and drug dynamics on the tissue scale. We aim to provide a theoretical setting for a better understanding of the design of effective anti-cancer therapies.

scholarly journals Impact of the Tumor Microenvironment on Tumor Heterogeneity and Consequences for Cancer Cell Plasticity and Stemness

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3716
Author(s):  
Ralf Hass ◽  
Juliane von der Ohe ◽  
Hendrik Ungefroren
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cell ◽  
Tumor Heterogeneity ◽  
Cancer Therapies ◽  
Epigenetic Alterations ◽  
Cell Plasticity ◽  
Cellular Phenotypes ◽  
Therapy Success ◽  
Physical And Chemical

Tumor heterogeneity is considered the major cause of treatment failure in current cancer therapies. This feature of solid tumors is not only the result of clonal outgrowth of cells with genetic mutations, but also of epigenetic alterations induced by physical and chemical signals from the tumor microenvironment (TME). Besides fibroblasts, endothelial and immune cells, mesenchymal stroma/stem-like cells (MSCs) and tumor-associated macrophages (TAMs) intimately crosstalk with cancer cells and can exhibit both anti- and pro-tumorigenic effects. MSCs can alter cancer cellular phenotypes to increase cancer cell plasticity, eventually resulting in the generation of cancer stem cells (CSCs). The shift between different phenotypic states (phenotype switching) of CSCs is controlled via both genetic programs, such as epithelial-mesenchymal transdifferentiation or retrodifferentiation, and epigenetic alterations triggered by signals from the TME, like hypoxia, spatial heterogeneity or stromal cell-derived chemokines. Finally, we highlight the role of spontaneous cancer cell fusion with various types of stromal cells. i.e., MSCs in shaping CSC plasticity. A better understanding of cell plasticity and phenotype shifting in CSCs is a prerequisite for exploiting this phenomenon to reduce tumor heterogeneity, thereby improving the chance for therapy success.

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