scholarly journals The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy?

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sonja S. Mojsilovic ◽  
Slavko Mojsilovic ◽  
Victor H. Villar ◽  
Juan F. Santibanez
Keyword(s):  
Cancer Progression ◽  
Tumor Tissue ◽  
Acid Metabolism ◽  
Cell Types ◽  
Innate Immune ◽  
High Plasticity ◽  
Tumor Associated Macrophages ◽  
Cell Therapies ◽  
Physical Barriers ◽  
Cancer Immunotherapies

Besides transformed cells, the tumors are composed of various cell types that contribute to undesirable tumor progression. Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in the tumor microenvironment (TME). Within the TME, TAMs exhibit high plasticity and undergo specific functional metabolic alterations according to the availability of tumor tissue oxygen and nutrients, thus further contributing to tumorigenesis and cancer progression. Here, we review the main functional TAM metabolic patterns influenced by TME, including glycolysis, amino acid, and fatty acid metabolism. Moreover, this review discusses antitumor immunotherapies that affect TAM functionality by inducing cell repolarizing and metabolic profiles towards an antitumoral phenotype. Also, new macrophage-based cell therapeutic technologies recently developed using chimeric antigen receptor bioengineering are exposed, which may overcome all solid tumor physical barriers impeding the current adoptive cell therapies and contribute to developing novel cancer immunotherapies.

scholarly journals Metabolism in tumour-associated macrophages: a quid pro quo with the tumour microenvironment

2020 ◽  
Vol 29 (157) ◽  
pp. 200134
Author(s):  
Xiang Zheng ◽  
Siavash Mansouri ◽  
Annika Krager ◽  
Friedrich Grimminger ◽  
Werner Seeger ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Acid Metabolism ◽  
Environmental Changes ◽  
Tumour Progression ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
High Plasticity ◽  
Functional Alteration

Lung cancer is the leading cause of death from cancer worldwide. Recent studies demonstrated that the tumour microenvironment (TME) is pivotal for tumour progression, providing multiple targeting opportunities for therapeutic strategies. As one of the most abundant stromal cell types in the TME, tumour-associated macrophages (TAMs) exhibit high plasticity. Malignant cells alter their metabolic profiles to adapt to the limited availability of oxygen and nutrients in the TME, resulting in functional alteration of TAMs. The metabolic features of TAMs are strongly associated with their functional plasticity, which further impacts metabolic profiling in the TME and contributes to tumourigenesis and progression. Here, we review the functional determination of the TME by TAM metabolic alterations, including glycolysis as well as fatty acid and amino acid metabolism, which in turn are influenced by environmental changes. Additionally, we discuss metabolic reprogramming of TAMs to a tumouricidal phenotype as a potential antitumoural therapeutic strategy.

scholarly journals MAPKAP Kinase-2 Drives Expression of Angiogenic Factors by Tumor-Associated Macrophages in a Model of Inflammation-Induced Colon Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lucia Suarez-Lopez ◽  
Yi Wen Kong ◽  
Ganapathy Sriram ◽  
Jesse C. Patterson ◽  
Samantha Rosenberg ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Chronic Inflammation ◽  
Cancer Progression ◽  
Tumor Angiogenesis ◽  
Cell Types ◽  
Adoptive Cell Transfer ◽  
Tumor Associated Macrophages

Chronic inflammation increases the risk for colorectal cancer through a variety of mechanisms involving the tumor microenvironment. MAPK-activated protein kinase 2 (MK2), a major effector of the p38 MAPK stress and DNA damage response signaling pathway, and a critical regulator of pro-inflammatory cytokine production, has been identified as a key contributor to colon tumorigenesis under conditions of chronic inflammation. We have previously described how genetic inactivation of MK2 in an inflammatory model of colon cancer results in delayed tumor progression, decreased tumor angiogenesis, and impaired macrophage differentiation into a pro-tumorigenic M2-like state. The molecular mechanism responsible for the impaired angiogenesis and tumor progression, however, has remained contentious and poorly defined. Here, using RNA expression analysis, assays of angiogenesis factors, genetic models, in vivo macrophage depletion and reconstitution of macrophage MK2 function using adoptive cell transfer, we demonstrate that MK2 activity in macrophages is necessary and sufficient for tumor angiogenesis during inflammation-induced cancer progression. We identify a critical and previously unappreciated role for MK2-dependent regulation of the well-known pro-angiogenesis factor CXCL-12/SDF-1 secreted by tumor associated-macrophages, in addition to MK2-dependent regulation of Serpin-E1/PAI-1 by several cell types within the tumor microenvironment.

scholarly journals Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 46 ◽  
Author(s):  
Anfray ◽  
Ummarino ◽  
Andón ◽  
Allavena
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Tumor Tissue ◽  
Tumor Response ◽  
Current Knowledge ◽  
Tumor Associated Macrophages ◽  
Cancer Proliferation ◽  
The Past ◽  
Active Research ◽  
Novel Therapeutic Strategies

: Established evidence demonstrates that tumor-infiltrating myeloid cells promote rather than stop-cancer progression. Tumor-associated macrophages (TAMs) are abundantly present at tumor sites, and here they support cancer proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Their pro-tumor activities hamper the response of cancer patients to conventional therapies, such as chemotherapy or radiotherapy, and also to immunotherapies based on checkpoint inhibition. Active research frontlines of the last years have investigated novel therapeutic strategies aimed at depleting TAMs and/or at reprogramming their tumor-promoting effects, with the goal of re-establishing a favorable immunological anti-tumor response within the tumor tissue. In recent years, numerous clinical trials have included pharmacological strategies to target TAMs alone or in combination with other therapies. This review summarizes the past and current knowledge available on experimental tumor models and human clinical studies targeting TAMs for cancer treatment.

scholarly journals Transcriptomic Analysis of the Innate Immune Response to in vitro Transfection of Plasmid DNA

2021 ◽  
Author(s):  
Eric Warga ◽  
Matthew Tucker ◽  
Emily Harris ◽  
Jacob Elmer
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Innate Immune Response ◽  
Viral Infections ◽  
Transfection Efficiency ◽  
Cell Types ◽  
Innate Immune ◽  
Nonviral Gene Delivery ◽  
Cell Therapies

The innate immune response to cytosolic DNA is intended to protect the host from viral infections, but it can also inhibit the delivery and expression of therapeutic transgenes in gene and cell therapies. The goal of this work was to use mRNA-sequencing to reveal correlations between the transfection efficiencies of four cell types (PC-3, Jurkat, HEK-293T, and primary CD3+ T cells) and their innate immune responses to nonviral gene delivery. Overall, the highest transfection efficiency was observed in HEK-293T cells (87%), which upregulated only 142 genes with no known anti-viral functions. Lipofection upregulated a much larger number (n = 1,057) of cytokine-stimulated genes (CSGs) in PC-3 cells, which also exhibited a significantly lower transfection efficiency. However, the addition of serum during Lipofection and electroporation significantly increased transfection efficiencies and decreased the number of upregulated genes in PC-3 cells. Finally, while Lipofection of Jurkat and Primary T cells only upregulated a few genes, several anti-viral CSGs that were absent in HEK and upregulated in PC-3 cells were observed to be constitutively expressed in T cells, which may explain their relatively low Lipofection efficiencies (8-21%). Indeed, overexpression of one such CSG (IFI16) significantly decreased transfection efficiency in HEK cells to 33%.

scholarly journals Tumor-Associated Macrophages: A Potential Target for Cancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Yifan Tan ◽  
Min Wang ◽  
Yang Zhang ◽  
Shengyang Ge ◽  
Fan Zhong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Malignant Tumors ◽  
Therapeutic Strategies ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Tumor Associated Macrophages ◽  
Supportive Role ◽  
High Degree ◽  
Significant Attention

Macrophages, an important class of innate immune cells that maintain body homeostasis and ward off foreign pathogens, exhibit a high degree of plasticity and play a supportive role in different tissues and organs. Thus, dysfunction of macrophages may contribute to advancement of several diseases, including cancer. Macrophages within the tumor microenvironment are known as tumor-associated macrophages (TAMs), which typically promote cancer cell initiation and proliferation, accelerate angiogenesis, and tame anti-tumor immunity to promote tumor progression and metastasis. Massive infiltration of TAMs or enrichment of TAM-related markers usually indicates cancer progression and a poor prognosis, and consequently tumor immunotherapies targeting TAMs have gained significant attention. Here, we review the interaction between TAMs and cancer cells, discuss the origin, differentiation and phenotype of TAMs, and highlight the role of TAMs in pro-cancer functions such as tumor initiation and development, invasive metastasis, and immunosuppression. Finally, we review therapies targeting TAMs, which are very promising therapeutic strategies for malignant tumors.

scholarly journals Tumor-Associated Macrophages: Combination of Therapies, the Approach to Improve Cancer Treatment

2021 ◽  
Vol 22 (13) ◽  
pp. 7239
Author(s):  
Pedram Moeini ◽  
Paulina Niedźwiedzka-Rystwej
Keyword(s):  
Immune System ◽  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Innate Immune System ◽  
Innate Immune ◽  
Tumor Associated Macrophages ◽  
Therapy Failure ◽  
Cellular Debris

Macrophages are one of the most important cells of the innate immune system and are known for their ability to engulf and digest foreign substances, including cellular debris and tumor cells. They can convert into tumor-associated macrophages (TAMs) when mature macrophages are recruited into the tumor microenvironment. Their role in cancer progression, metastasis, and therapy failure is of special note. The aim of this review is to understand how the presence of TAMs are both advantageous and disadvantageous in the immune system.

scholarly journals Fatty Acid Metabolism in Myeloid-Derived Suppressor Cells and Tumor-Associated Macrophages: Key Factor in Cancer Immune Evasion

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 250
Author(s):  
Sophiya Siddiqui ◽  
Rainer Glauben
Keyword(s):  
Fatty Acids ◽  
Cancer Progression ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Cell Types ◽  
Eukaryotic Cell ◽  
Metabolic Reprogramming ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Associated Macrophages ◽  
Key Factor

The tumor microenvironment (TME) comprises various cell types, soluble factors, viz, metabolites or cytokines, which together play in promoting tumor metastasis. Tumor infiltrating immune cells play an important role against cancer, and metabolic switching in immune cells has been shown to affect activation, differentiation, and polarization from tumor suppressive into immune suppressive phenotypes. Macrophages represent one of the major immune infiltrates into TME. Blood monocyte-derived macrophages and myeloid derived suppressor cells (MDSCs) infiltrating into the TME potentiate hostile tumor progression by polarizing into immunosuppressive tumor-associated macrophages (TAMs). Recent studies in the field of immunometabolism focus on metabolic reprogramming at the TME in polarizing tumor-associated macrophages (TAMs). Lipid droplets (LD), detected in almost every eukaryotic cell type, represent the major source for intra-cellular fatty acids. Previously, LDs were mainly described as storage sites for fatty acids. However, LDs are now recognized to play an integral role in cellular signaling and consequently in inflammation and metabolism-mediated phenotypical changes in immune cells. In recent years, the role of LD dependent metabolism in macrophage functionality and phenotype has been being investigated. In this review article, we discuss fatty acids stored in LDs, their role in modulating metabolism of tumor-infiltrating immune cells and, therefore, in shaping the cancer progression.

scholarly journals Specialized Pro-Resolving Mediators Mitigate Cancer-Related Inflammation: Role of Tumor-Associated Macrophages and Therapeutic Opportunities

2021 ◽  
Vol 12 ◽  
Author(s):  
Margot Lavy ◽  
Vanessa Gauttier ◽  
Nicolas Poirier ◽  
Sophie Barillé-Nion ◽  
Christophe Blanquart
Keyword(s):  
Cancer Therapy ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Immune Escape ◽  
Therapy Resistance ◽  
High Plasticity ◽  
Tumor Cell Death ◽  
Tumor Associated Macrophages ◽  
Inflammation Resolution

Inflammation is a fundamental physiological response orchestrated by innate immune cells to restore tissue homeostasis. Specialized pro-resolving mediators (SPMs) are involved in active resolution of inflammation but when inflammation is incomplete, chronic inflammation creates a favorable environment that fuels carcinogenesis and cancer progression. Conventional cancer therapy also strengthens cancer-related inflammation by inducing massive tumor cell death that activate surrounding immune-infiltrating cells such as tumor-associated macrophages (TAMs). Macrophages are key actors of both inflammation and its active resolution due to their plastic phenotype. In line with this high plasticity, macrophages can be hijacked by cancer cells to support tumor progression and immune escape, or therapy resistance. Impaired resolution of cancer-associated inflammation supported by TAMs may thus reinforces tumor progression. From this perspective, recent evidence suggests that stimulating macrophage’s pro-resolving functions using SPMs can promote inflammation resolution in cancer and improve anticancer treatments. Thus, TAMs’ re-education toward an antitumor phenotype by using SPMs opens a new line of attack in cancer treatment. Here, we review SPMs’ anticancer capacities with special attention regarding their effects on TAMs. We further discuss how this new therapeutic approach could be envisioned in cancer therapy.

scholarly journals Tumor associated macrophages: current research and perspectives of clinical use

2019 ◽  
Vol 5 (4) ◽  
pp. 20-28
Author(s):  
A. N. Gratchev ◽  
D. V. Samoilova ◽  
M. A. Rashidova ◽  
A. A. Petrenko ◽  
O. V. Kovaleva
Keyword(s):  
Growth Factors ◽  
Vascular System ◽  
Cell Transformation ◽  
Tumor Development ◽  
Cell Types ◽  
Innate Immune ◽  
Tumor Associated Macrophages ◽  
Effective Response ◽  
Extracellular Matrix Components

Macrophages are the key cells of the innate immune system. One of the main functions of macrophages is the regulation of inflammation. Being common in all tissues and organs of the human body, tissue macrophages control their condition and guarantee a timely and effective response to damage, pathogen penetration or cell transformation. After eliminating the cause of inflammation, macrophages initiate the processes of healing and restoration of tissue homeostasis. At the end of the 20thcentury, the concept of macrophage activation dichotomy was proposed, which divided them into classically (M1) and alternatively (M2) activated ones. The development of this concept has led to the description of a wide variety of macrophage phenotypes. At the same time, M2 continues to be considered a prototype of tumor associated macrophages (TAM).TAM represent one of the most important cell types in the tumor microenvironment. Like all macrophages, they have a certain level of heterogeneity and plasticity, which develop under the influence of cytokines and growth factors produced by tumor cells. TAM, in turn, produces growth factors, cytokines and extracellular matrix components that support the progression of the tumor and increase its malignant potential. Numerous clinical studies have shown that the amount of TAM is often correlated with a poor prognosis of the disease. TAM perform a large number of functions necessary to maintain tumor progression. They are capable of stimulating angiogenesis and reorganization of the vascular system. Since the role of TAM in tumor development has become apparent, various attempts have been made to use them in the clinic.  It can be confidently asserted that various TAM markers are very attractive as diagnostic and prognostic markers of various tumors, and also as promising targets for the development of new targeted therapeutic agents.

Endometrial Regeneration in Asherman's Syndrome: Clinical and Translational evidence of Stem Cell Therapies

2019 ◽  
Vol 14 (6) ◽  
pp. 454-459
Author(s):  
Xuejing Hou ◽  
Ying Liu ◽  
Isabelle Streuli ◽  
Patrick Dällenbach ◽  
Jean Dubuisson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Molecular Mechanisms ◽  
Uterine Cavity ◽  
Stem Cell Therapies ◽  
Intrauterine Adhesions ◽  
Asherman’S Syndrome ◽  
Cell Therapies ◽  
Fibrotic Process ◽  
Physical Barriers

Asherman’s Syndrome or Intrauterine adhesions is an acquired uterine condition where fibrous scarring forms within the uterine cavity, resulting in reduced menstrual flow, pelvic pain and infertility. Until recently, the molecular mechanisms leading to the formation of fibrosis were poorly understood, and the treatment of Asherman’s syndrome has largely focused on hysteroscopic resection of adhesions, hormonal therapy, and physical barriers. Numerous studies have begun exploring the molecular mechanisms behind the fibrotic process underlying Asherman’s Syndrome as well as the role of stem cells in the regeneration of the endometrium as a treatment modality. The present review offers a summary of available stem cell-based regeneration studies, as well as highlighting current gaps in research.

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