scholarly journals Tumor-Associated Macrophages and Their Functional Transformation in the Hypoxic Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Zicong He ◽  
Shuixing Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Tumor Associated Macrophages ◽  
Mediate Immune Response ◽  
Functional Transformation ◽  
Functional Differences ◽  
Inflammatory Phenotype ◽  
Internal Mechanism ◽  
Hypoxic Tumor ◽  
Early Phases

Tumor-associated macrophages (TAMs) are some of the most abundant immune cells within tumors and perform a broad repertoire of functions via diverse phenotypes. On the basis of their functional differences in tumor growth, TAMs are usually categorized into two subsets of M1 and M2. It is well established that the tumor microenvironment (TME) is characterized by hypoxia along with tumor progression. TAMs adopt an M1-like pro-inflammatory phenotype at the early phases of oncogenesis and mediate immune response that inhibits tumor growth. As tumors progress, anabatic hypoxia of the TME gradually induces the M2-like functional transformation of TAMs by means of direct effects, metabolic influence, lactic acidosis, angiogenesis, remodeled stroma, and then urges them to participate in immunosuppression, angiogenesis and other tumor-supporting procedure. Therefore, thorough comprehension of internal mechanism of this TAM functional transformation in the hypoxic TME is of the essence, and might provide some novel insights in hypoxic tumor immunotherapeutic strategies.

scholarly journals The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

2018 ◽  
Vol 45 (1) ◽  
pp. 356-365 ◽  
Author(s):  
Xiaoming Zhong ◽  
Bin Chen ◽  
Zhiwen Yang
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Colorectal Carcinoma ◽  
Tumor Growth ◽  
Immune Cells ◽  
Strong Evidence ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Tumor Associated Macrophages

Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the tumor microenvironment, and they play a pivotal role in prompting the various tumor growth. However, the role of TAMs in colorectal carcinoma (CRC) is controversial, because a few papers report that TAMs is beneficial to CRC patients. In this review, we discuss the good or bad roles of TAMs in CRC progression. Interestingly, recent studies provide strong evidence that TAMs facilitate CRC growth, but do not exert tumor suppressive activities. TAMs can stimulate CRC growth by altering extracellular matrix remodeling, tumor metabolism, angiogenesis, as well as the tumor microenvironment. Therefore, TAMs could serve as a target for CRC therapeutic treatment.

scholarly journals Differential Polarization of Tumor-Associated Macrophages/Microglia Drives the Aggressiveness of Gliomas

2021 ◽  
Author(s):  
Nai-Wei Yao ◽  
Hsiu-Ting Lin ◽  
Ya-Lin Lin ◽  
Khamushavalli Geeviman ◽  
Fang Liao ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Wistar Rats ◽  
Tumor Development ◽  
C6 Glioma ◽  
Sprague Dawley ◽  
Tumor Associated Macrophages ◽  
Sd Rats ◽  
Glioma Growth

Abstract Background: Glioblastoma is the most aggressive subtype of brain tumors. The major component of tumor microenvironment in glioblastoma is tumor-associated macrophages (TAMs), which are associated with enhanced malignancy of glioblastoma. The polarization of macrophages to the pro-inflammatory M1 or anti-inflammatory M2 subtypes governed by the context of tumor microenvironment may dictate the aggressiveness and outcome of glioblastoma. Given that the immune responses to tumors vary distinctively among individuals due to intrinsic, environmental and genetic factors and that TAMs display a high level of diversity and plasticity, we aimed to examine the effects of differential polarization of TAMs on the glioblastoma development by implanting C6 glioma into brains of Sprague–Dawley (SD) and Wistar rats; these two rats have different genetic background and host microenvironment during tumor development. Methods: Sprague–Dawley (SD) and Wistar rats were implanted with C6 glioma in the brain. The measurement of tumor volumes, tumor morphology and tumor growth in C6 glioma implanted brains were measured by multi-parametric magnetic resonance imaging (MRI). Immunofluorescence staining was performed to analyze tumor angiogenesis and M1 and M2 TAMs in C6 gliomas. Results: By multi-parametric MRI measurement, C6 gliomas developed in the SD rats were characterized with enlarged tumors, accompanied with shorter animal survival. In comparison to the gliomas in Wistar rats, the accelerated tumor growth in SD rats was associated with greater extent of angiogenesis accompanied with higher levels of VEGF/VEGFR2. In support, C6 gliomas in SD rats were filtrated with TAMs characterized with a higher M2/M1 ratio, in contrast to the TAMs of a high M1/M2 ratio in Wistar rats. Attempts were made to shift the M2/M1 balance. Administration of the cytokine IFN-γ that induces M1 TAMs to SD rats greatly suppressed glioma formation, accompanied with a remarkable increase of M1 TAMs. Administration of the cytokines IL-4 plus IL-10 that induces M2 TAMs significantly promoted glioma growth in the Wistar rats, associated with an increase in the M2 TAMs. Conclusions: These results demonstrate an important role of TAMs in glioma pathogenesis and the crucial role of microenvironment in dictating the polarization of TAMs, suggesting that targeting or repolarization of TAMs may serve as an effective intervention for gliomas.

M2 polarization of macrophages by Oncostatin M in hypoxic tumor microenvironment is mediated by mTORC2 and promotes tumor growth and metastasis

Cytokine ◽  
2019 ◽  
Vol 118 ◽  
pp. 130-143 ◽  
Author(s):  
Richa Shrivastava ◽  
Mohammad Asif ◽  
Varsha Singh ◽  
Parul Dubey ◽  
Showkat Ahmad Malik ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Oncostatin M ◽  
M2 Polarization ◽  
Hypoxic Tumor ◽  
Tumor Growth And Metastasis

Supramolecular nanovesicles for synergistic glucose starvation and hypoxia-activated gene therapy of cancer

Nanoscale ◽  
2021 ◽  
Author(s):  
Ludan Yue ◽  
Tianlei Sun ◽  
Kuikun Yang ◽  
Qian Cheng ◽  
Junyan Li ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tumor Microenvironment ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Therapeutic Strategy ◽  
Glucose Starvation ◽  
Inhibit Tumor Growth ◽  
Hypoxic Tumor

Glucose starvation has emerged as a therapeutic strategy to inhibit tumor growth by regulating glucose metabolism. However, the rapid proliferation of cancer cells could induce the hypoxic tumor microenvironment (TME)...

scholarly journals 695 Oral delivery of a microbial extracellular vesicle induces potent anti-tumor immunity in mice

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A737-A737
Author(s):  
Loise Francisco-Anderson ◽  
Loise Francisco-Anderson ◽  
Mary Abdou ◽  
Michael Goldberg ◽  
Erin Troy ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Extracellular Vesicles ◽  
Tumor Immunity ◽  
Extracellular Vesicle ◽  
The Body ◽  
Checkpoint Inhibition ◽  
Small Intestinal ◽  
The Impact

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.

scholarly journals A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Farias ◽  
A. Soto ◽  
F. Puttur ◽  
C. J. Goldin ◽  
S. Sosa ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Therapeutic Effect ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Combined Treatment ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Regulatory Cells ◽  
Ifn Γ

AbstractBrucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells via toll like receptor 4, inducing the secretion of pro-inflammatory cytokines and chemokines. We have previously shown that BLS has a therapeutic effect in B16 melanoma-bearing mice only when administered at early stages of tumor growth. In this work, we study the mechanisms underlying the therapeutic effect of BLS, by analyzing the tumor microenvironment. Administration of BLS at early stages of tumor growth induces high levels of serum IFN-γ, as well as an increment of hematopoietic immune cells within the tumor. Moreover, BLS-treatment increases the ratio of effector to regulatory cells. However, all treated mice eventually succumb to the tumors. Therefore, we combined BLS administration with anti-PD-1 treatment. Combined treatment increases the outcome of both monotherapies. In conclusion, we show that the absence of the therapeutic effect at late stages of tumor growth correlates with low levels of serum IFN-γ and lower infiltration of immune cells in the tumor, both of which are essential to delay tumor growth. Furthermore, the combined treatment of BLS and PD-1 blockade shows that BLS could be exploited as an essential immunomodulator in combination therapy with an immune checkpoint blockade to treat skin cancer.

scholarly journals Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer

2021 ◽  
Vol 9 (1) ◽  
pp. e001341
Author(s):  
Chunxiao Li ◽  
Xiaofei Xu ◽  
Shuhua Wei ◽  
Ping Jiang ◽  
Lixiang Xue ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Tumor Immunotherapy ◽  
Therapeutic Strategies ◽  
Preclinical Studies ◽  
Future Prospects ◽  
Tumor Associated Macrophages

Macrophages are the most important phagocytes in vivo. However, the tumor microenvironment can affect the function and polarization of macrophages and form tumor-associated macrophages (TAMs). Usually, the abundance of TAMs in tumors is closely associated with poor prognosis. Preclinical studies have identified important pathways regulating the infiltration and polarization of TAMs during tumor progression. Furthermore, potential therapeutic strategies targeting TAMs in tumors have been studied, including inhibition of macrophage recruitment to tumors, functional repolarization of TAMs toward an antitumor phenotype, and other therapeutic strategies that elicit macrophage-mediated extracellular phagocytosis and intracellular destruction of cancer cells. Therefore, with the increasing impact of tumor immunotherapy, new antitumor strategies to target TAMs are now being discussed.

scholarly journals Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma

2021 ◽  
Vol 22 (7) ◽  
pp. 3578
Author(s):  
Federico Armando ◽  
Adnan Fayyad ◽  
Stefanie Arms ◽  
Yvonne Barthel ◽  
Dirk Schaudien ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Virus Infection ◽  
Tumor Growth ◽  
Canine Distemper Virus ◽  
Xenograft Model ◽  
Histiocytic Sarcoma ◽  
Oncolytic Viruses ◽  
Canine Distemper ◽  
Murine Xenograft Model ◽  
The Impact

Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.

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