scholarly journals The Role of Macrophages in Cancer Development and Therapy

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1946
Author(s):  
Ewa Cendrowicz ◽  
Zuzanna Sas ◽  
Edwin Bremer ◽  
Tomasz P. Rygiel
Keyword(s):  
Cancer Cell ◽  
Strong Association ◽  
Tumor Development ◽  
Therapeutic Approaches ◽  
Cell Recruitment ◽  
Patient Prognosis ◽  
And Function ◽  
Cellular Components ◽  
Activation Status

Macrophages are critical mediators of tissue homeostasis and influence various aspects of immunity. Tumor-associated macrophages are one of the main cellular components of the tumor microenvironment. Depending on their activation status, macrophages can exert a dual influence on tumorigenesis by either antagonizing the cytotoxic activity of immune cells or, less frequently, by enhancing antitumor responses. In most situations, TAMs suppress T cell recruitment and function or regulate other aspects of tumor immunity. The importance of TAMs targeting in cancer therapy is derived from the strong association between the high infiltration of TAMs in the tumor tissue with poor patient prognosis. Several macrophage-targeting approaches in anticancer therapy are developed, including TAM depletion, inhibition of new TAM differentiation, or re-education of TAM activation for cancer cell phagocytosis. In this review, we will describe the role of TAMs in tumor development, including such aspects as protumorigenic inflammation, immune suppression, neoangiogenesis, and enhancement of tissue invasion and distant metastasis. Furthermore, we will discuss therapeutic approaches that aim to deplete TAMs or, on the contrary, re-educate TAMs for cancer cell phagocytosis and antitumor immunity.

scholarly journals Autophagy Function and Regulation in Kidney Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 100 ◽  
Author(s):  
Gur P. Kaushal ◽  
Kiran Chandrashekar ◽  
Luis A. Juncos ◽  
Sudhir V. Shah
Keyword(s):  
Cell Death ◽  
Renal Injury ◽  
Mammalian Target Of Rapamycin ◽  
Kidney Injury ◽  
Therapeutic Approaches ◽  
Regulated Necrosis ◽  
Atg Genes ◽  
Cellular Components ◽  
The Impact

Autophagy is a dynamic process by which intracellular damaged macromolecules and organelles are degraded and recycled for the synthesis of new cellular components. Basal autophagy in the kidney acts as a quality control system and is vital for cellular metabolic and organelle homeostasis. Under pathological conditions, autophagy facilitates cellular adaptation; however, activation of autophagy in response to renal injury may be insufficient to provide protection, especially under dysregulated conditions. Kidney-specific deletion of Atg genes in mice has consistently demonstrated worsened acute kidney injury (AKI) outcomes supporting the notion of a pro-survival role of autophagy. Recent studies have also begun to unfold the role of autophagy in progressive renal disease and subsequent fibrosis. Autophagy also influences tubular cell death in renal injury. In this review, we reported the current understanding of autophagy regulation and its role in the pathogenesis of renal injury. In particular, the classic mammalian target of rapamycin (mTOR)-dependent signaling pathway and other mTOR-independent alternative signaling pathways of autophagy regulation were described. Finally, we summarized the impact of autophagy activation on different forms of cell death, including apoptosis and regulated necrosis, associated with the pathophysiology of renal injury. Understanding the regulatory mechanisms of autophagy would identify important targets for therapeutic approaches.

scholarly journals Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors

2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 8-11 ◽  
Author(s):  
Paola Nisticò ◽  
Gennaro Ciliberto
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Tumor Development ◽  
Short Paper ◽  
Great Relevance ◽  
Cellular Components ◽  
The Relationship

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.

scholarly journals Far from Health: The Bone Marrow Microenvironment in AML, A Leukemia Supportive Shelter

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 371
Author(s):  
Stephanie Sendker ◽  
Katharina Waack ◽  
Dirk Reinhardt
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Bone Marrow Microenvironment ◽  
Leukemic Cells ◽  
Therapeutic Approaches ◽  
Complex Interplay ◽  
Comprehensive Overview ◽  
Future Challenges ◽  
Cellular Components

Acute myeloid leukemia (AML) is the second most common leukemia among children. Although significant progress in AML therapy has been achieved, treatment failure is still associated with poor prognosis, emphasizing the need for novel, innovative therapeutic approaches. To address this major obstacle, extensive knowledge about leukemogenesis and the complex interplay between leukemic cells and their microenvironment is required. The tremendous role of this bone marrow microenvironment in providing a supportive and protective shelter for leukemic cells, leading to disease development, progression, and relapse, has been emphasized by recent research. It has been revealed that the interplay between leukemic cells and surrounding cellular as well as non-cellular components is critical in the process of leukemogenesis. In this review, we provide a comprehensive overview of recently gained knowledge about the importance of the microenvironment in AML whilst focusing on promising future therapeutic targets. In this context, we describe ongoing clinical trials and future challenges for the development of targeted therapies for AML.

scholarly journals The conformational and mutational landscape of the ubiquitin-like marker for the autophagosome formation in cancer

2019 ◽  
Author(s):  
Burcu Aykac Fas ◽  
Mukesh Kumar ◽  
Valentina Sora ◽  
Maliha Mashkoor ◽  
Matteo Lambrughi ◽  
...  
Keyword(s):  
Physical Models ◽  
Missense Mutations ◽  
Cancer Types ◽  
Neutral Mutations ◽  
And Function ◽  
Cellular Components ◽  
The Impact ◽  
Pan Cancer ◽  
Structural Ensemble

AbstractAutophagy is a cellular process to recycle damaged cellular components and its modulation can be exploited for disease treatments. A key autophagy player is a ubiquitin-like protein, LC3B. Compelling evidence attests the role of autophagy and LC3B in different cancer types. Many LC3B structures have been solved, but a comprehensive study, including dynamics, has not been yet undertaken. To address this knowledge gap, we assessed ten physical models for molecular dynamics for their capabilities to describe the structural ensemble of LC3B in solution using different metrics and comparison with NMR data. With the resulting LC3B ensembles, we characterized the impact of 26 missense mutations from Pan-Cancer studies with different approaches. Our findings shed light on driver or neutral mutations in LC3B, providing an atlas of its modifications in cancer. Our framework could be used to assess the pathogenicity of mutations by accounting for the different aspects of protein structure and function altered by mutational events.

scholarly journals Application of Single-Cell Multi-Omics in Dissecting Cancer Cell Plasticity and Tumor Heterogeneity

2021 ◽  
Vol 8 ◽  
Author(s):  
Deshen Pan ◽  
Deshui Jia
Keyword(s):  
Single Cell ◽  
Cancer Cell ◽  
Tumor Heterogeneity ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Tumor Development ◽  
Cell Plasticity ◽  
Translational Cancer Research ◽  
Cellular Components

Tumor heterogeneity, a hallmark of cancer, impairs the efficacy of cancer therapy and drives tumor progression. Exploring inter- and intra-tumoral heterogeneity not only provides insights into tumor development and progression, but also guides the design of personalized therapies. Previously, high-throughput sequencing techniques have been used to investigate the heterogeneity of tumor ecosystems. However, they could not provide a high-resolution landscape of cellular components in tumor ecosystem. Recently, advance in single-cell technologies has provided an unprecedented resolution to uncover the intra-tumoral heterogeneity by profiling the transcriptomes, genomes, proteomes and epigenomes of the cellular components and also their spatial distribution, which greatly accelerated the process of basic and translational cancer research. Importantly, it has been demonstrated that some cancer cells are able to transit between different states in order to adapt to the changing tumor microenvironment, which led to increased cellular plasticity and tumor heterogeneity. Understanding the molecular mechanisms driving cancer cell plasticity is critical for developing precision therapies. In this review, we summarize the recent progress in dissecting the cancer cell plasticity and tumor heterogeneity by use of single-cell multi-omics techniques.

scholarly journals Histone H2B as a functionally important plasminogen receptor on macrophages

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3763-3772 ◽  
Author(s):  
Riku Das ◽  
Tim Burke ◽  
Edward F. Plow
Keyword(s):  
Binding Capacity ◽  
Peritoneal Macrophages ◽  
Blood Monocytes ◽  
Histone H2b ◽  
Cell Recruitment ◽  
Annexin 2 ◽  
Enhanced Expression ◽  
And Function ◽  
Mouse Peritoneal Macrophages

AbstractPlasminogen (Plg) facilitates inflammatory cell recruitment, a function that depends upon its binding to Plg receptors (Plg-Rs). However, the Plg-Rs that are critical for cell migration are not well defined. Three previously characterized Plg-Rs (α-enolase, annexin 2, and p11) and a recently identified Plg-R (histone H2B [H2B]) were assessed for their contribution to Plg binding and function on macrophages. Two murine macrophage cell lines (RAW 264.7 and J774A.1) and mouse peritoneal macrophages induced by thioglycollate were analyzed. All 4 Plg-Rs were present on the surface of these cells and showed enhanced expression on the thioglycollate-induced macrophages compared with peripheral blood monocytes. Using blocking Fab fragments to each Plg-R, H2B supported approximately 50% of the Plg binding capacity, whereas the other Plg-Rs contributed less than 25%. Anti-H2B Fab also demonstrated a major role of this Plg-R in plasmin generation and matrix invasion. When mice were treated intravenously with anti-H2B Fab, peritoneal macrophage recruitment in response to thioglycollate was reduced by approximately 45% at 24, 48, and 72 hours, with no effect on blood monocyte levels. Taken together, these data suggest that multiple Plg-Rs do contribute to Plg binding to macrophages, and among these, H2B plays a very prominent and functionally important role.

Cancer Immunology and Immuno-Oncology (Innate vs. Adaptive Cell Immunity)

2020 ◽  
Author(s):  
Nariman Nezami ◽  
Carlos J. Sanchez ◽  
John Moon ◽  
Jamil Shaikh ◽  
Nima Kokabi
Keyword(s):  
Immune System ◽  
Tumor Microenvironment ◽  
Tumor Metastasis ◽  
Tumor Development ◽  
Genetic Changes ◽  
Complex Interactions ◽  
Cell Immunity ◽  
Complex Ecosystem ◽  
Cellular Components

AbstractTumorigenesis occurs due to both intrinsic cellular genetic changes and imbalances within the tumor microenvironment. This microenvironment is composed of a complex ecosystem of tumor cells, vasculature, extracellular matrix, stromal cells, and immune cells. With these cells, there is both immune activation and immune suppression that promote or inhibit tumor development. These interactions lead to a constant flux of remodeling within the tumor microenvironment that additionally promote or inhibits tumor metastasis. To promote or suppress either antitumorigenic or protumorigenic effects, it is important to understand the complex interactions of the tumor and its interactions with the immune system within the tumor microenvironment. This review article addresses the role of the immune system and its cellular components within the tumor microenvironment.

scholarly journals Emerging Concepts and Functions of Autophagy as a Regulator of Synaptic Components and Plasticity

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 34 ◽  
Author(s):  
YongTian Liang
Keyword(s):  
Synaptic Plasticity ◽  
Protein Interactions ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Protein Protein Interactions ◽  
Neuronal Function ◽  
And Function ◽  
Cellular Components ◽  
Neuronal Autophagy

Protein homeostasis (proteostasis) is crucial to the maintenance of neuronal integrity and function. As the contact sites between neurons, synapses rely heavily on precisely regulated protein-protein interactions to support synaptic transmission and plasticity processes. Autophagy is an effective degradative pathway that can digest cellular components and maintain cellular proteostasis. Perturbations of autophagy have been implicated in aging and neurodegeneration due to a failure to remove damaged proteins and defective organelles. Recent evidence has demonstrated that autophagosome formation is prominent at synaptic terminals and neuronal autophagy is regulated in a compartment-specific fashion. Moreover, synaptic components including synaptic proteins and vesicles, postsynaptic receptors and synaptic mitochondria are known to be degraded by autophagy, thereby contributing to the remodeling of synapses. Indeed, emerging studies indicate that modulation of autophagy may be required for different forms of synaptic plasticity and memory formation. In this review, I will discuss our current understanding of the important role of neuronal/synaptic autophagy in maintaining neuronal function by degrading synaptic components and try to propose a conceptual framework of how the degradation of synaptic components via autophagy might impact synaptic function and contribute to synaptic plasticity.

scholarly journals Understanding PDE4's function in Alzheimer's disease; a target for novel therapeutic approaches

2019 ◽  
Vol 47 (5) ◽  
pp. 1557-1565 ◽  
Author(s):  
Amy J. Tibbo ◽  
Gonzalo S. Tejeda ◽  
George S. Baillie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Camp Response Element Binding ◽  
Cellular Tissue ◽  
Therapeutic Approaches ◽  
Camp Response Element ◽  
Age Related ◽  
Expression Activity ◽  
Activation Status

Abstract Phosphodiesterases (PDEs) have long been considered as targets for the treatment of Alzheimer's disease (AD) and a substantial body of evidence suggests that one sub-family from the super-family of PDEs, namely PDE4D, has particular significance in this context. This review discusses the role of PDE4 in the orchestration of cAMP response element binding signaling in AD and outlines the benefits of targeting PDE4D specifically. We examine the limited available literature that suggests PDE4 expression does not change in AD brains together with reports that show PDE4 inhibition as an effective treatment in this age-related neurodegenerative disease. Actually, aging induces changes in PDE4 expression/activity in an isoform and brain-region specific manner that proposes a similar complexity in AD brains. Therefore, a more detailed account of AD-related alterations in cellular/tissue location and the activation status of PDE4 is required before novel therapies can be developed to target cAMP signaling in this disease.

scholarly journals Inflammation in Periodontal Disease: Possible Link to Vascular Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Oindrila Paul ◽  
Payal Arora ◽  
Michael Mayer ◽  
Shampa Chatterjee
Keyword(s):  
Periodontal Disease ◽  
Bacterial Infections ◽  
Immune Cell ◽  
Epidemiological Data ◽  
Cell Recruitment ◽  
Periodontal Inflammation ◽  
Tissue Healing ◽  
And Function ◽  
Immune Cell Recruitment

Inflammation is a well-organized protective response to pathogens and consists of immune cell recruitment into areas of infection. Inflammation either clears pathogens and gets resolved leading to tissue healing or remains predominantly unresolved triggering pathological processes in organs. Periodontal disease (PD) that is initiated by specific bacteria also triggers production of inflammatory mediators. These processes lead to loss of tissue structure and function. Reactive oxygen species and oxidative stress play a role in susceptibility to periodontal pathogenic bacterial infections. Periodontal inflammation is a risk factor for systemic inflammation and eventually cardiovascular disease (CVD). This review discusses the role of inflammation in PD and its two way association with other health conditions such as diabetes and CVD. Some of the mechanisms underpinning the links between inflammation, diabetes, CVD and PD are also discussed. Finally, we review available epidemiological data and other reports to assess possible links between oral health and CVD.

Sign in / Sign up

Export Citation Format

Share Document