scholarly journals Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

2019 ◽  
Vol 20 (13) ◽  
pp. 3212 ◽  
Author(s):  
Magdalena Jarosz-Biej ◽  
Ryszard Smolarczyk ◽  
Tomasz Cichoń ◽  
Natalia Kułach
Keyword(s):  
Immune System ◽  
Tumor Microenvironment ◽  
Blood Vessels ◽  
Tumor Hypoxia ◽  
Suppressor Cells ◽  
Anticancer Efficacy ◽  
Anti Cancer ◽  
Radiation Induced ◽  
Game Changer

Radiotherapy (RT), besides cancer cells, also affects the tumor microenvironment (TME): tumor blood vessels and cells of the immune system. It damages endothelial cells and causes radiation-induced inflammation. Damaged vessels inhibit the infiltration of CD8+ T lymphocytes into tumors, and immunosuppressive pathways are activated. They lead to the accumulation of radioresistant suppressor cells, including tumor-associated macrophages (TAMs) with the M2 phenotype, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). The area of tumor hypoxia increases. Hypoxia reduces oxygen-dependent DNA damage and weakens the anti-cancer RT effect. It activates the formation of new blood vessels and leads to cancer relapse after irradiation. Irradiation may also activate the immune response through immunogenic cell death induction. This leads to the “in situ” vaccination effect. In this article, we review how changes in the TME affect radiation-induced anticancer efficacy. There is a very delicate balance between the activation of the immune system and the immunosuppression induced by RT. The effects of RT doses on immune system reactions and also on tumor vascularization remain unclear. A better understanding of these interactions will contribute to the optimization of RT treatment, which may prevent the recurrence of cancer.

Metabolic changes and interaction of tumor cell, myeloid-derived suppressor cell and T cell in hypoxic microenvironment

2020 ◽  
Author(s):  
Xiantu Ou ◽  
Weibiao Lv
Keyword(s):  
Tumor Microenvironment ◽  
Regulatory Protein ◽  
Tumor Hypoxia ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Inflammatory Factors ◽  
Tumor Escape ◽  
Myeloid Derived Suppressor Cells ◽  
Myeloid Derived Suppressor Cell ◽  
Transcriptional Regulatory

It is universally acknowledged that a large number of immune cells, as well as inflammatory factors, regulatory factors and metabolites, accumulate in the tumor microenvironment to jointly promote tumor escape, development and metastasis. Hypoxia is one of the characteristics in tumor microenvironment and is a common phenomenon in all solid tumors. In tumor hypoxia response, there is a key regulator called HIF-1a, which is a key transcriptional regulatory protein that regulates many critical genes. In this paper, the effects of hypoxia on glucose metabolism of tumor cells, myeloid-derived suppressor cells and T cells in tumor microenvironment were reviewed, and the interaction among the three was also described.

scholarly journals Immunological Evasion in Glioblastoma

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Roxana Magaña-Maldonado ◽  
Elda Georgina Chávez-Cortez ◽  
Nora Karen Olascoaga-Arellano ◽  
Mariana López-Mejía ◽  
Fernando Manuel Maldonado-Leal ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Immune Evasion ◽  
Suppressor Cells ◽  
M2 Macrophages ◽  
Effective Response ◽  
Aggressive Tumor

Glioblastoma is the most aggressive tumor in Central Nervous System in adults. Among its features, modulation of immune system stands out. Although immune system is capable of detecting and eliminating tumor cells mainly by cytotoxic T and NK cells, tumor microenvironment suppresses an effective response through recruitment of modulator cells such as regulatory T cells, monocyte-derived suppressor cells, M2 macrophages, and microglia as well as secretion of immunomodulators including IL-6, IL-10, CSF-1, TGF-β, and CCL2. Other mechanisms that induce immunosuppression include enzymes as indolamine 2,3-dioxygenase. For this reason it is important to develop new therapies that avoid this immune evasion to promote an effective response against glioblastoma.

scholarly journals Immunotherapy Targeting Myeloid-Derived Suppressor Cells (MDSCs) in Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Xidan Gao ◽  
Hongshu Sui ◽  
Shang Zhao ◽  
Xingmei Gao ◽  
Yanping Su ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Microenvironment ◽  
Immune Escape ◽  
Suppressor Cells ◽  
Tumor Immunotherapy ◽  
Therapeutic Effects ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Immune Escape ◽  
New Directions ◽  
Immature Myeloid Cells

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate in tumor-bearing hosts to reduce T cells activity and promote tumor immune escape in the tumor microenvironment (TME). The immune system in the TME can be stimulated to elicit an anti-tumor immune response through immunotherapy. The main theory of immunotherapy resides on the plasticity of the immune system and its capacity to be re-educated into a potent anti-tumor response. Thus, MDSCs within the TME became one of the major targets to improve the efficacy of tumor immunotherapy, and therapeutic strategies for tumor MDSCs were developed in the last few years. In the article, we analyzed the function of tumor MDSCs and the regulatory mechanisms of agents targeting MDSCs in tumor immunotherapy, and reviewed their therapeutic effects in MDSCs within the TME. Those data focused on discussing how to promote the differentiation and maturation of MDSCs, reduce the accumulation and expansion of MDSCs, and inhibit the function, migration and recruitment of MDSCs, further preventing the growth, invasion and metastasis of tumor. Those investigations may provide new directions for cancer therapy.

scholarly journals Targeting the MDSCs of Tumors In Situ With Inhibitors of the MAPK Signaling Pathway to Promote Tumor Regression

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiayun Yu ◽  
Hanwen Li ◽  
Zongliang Zhang ◽  
Weimin Lin ◽  
Xiawei Wei ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Protein Kinases ◽  
Tumor Regression ◽  
Suppressor Cells ◽  
Mapk Signaling ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Myeloid-derived suppressor cells (MDSCs) are one of the major components of the tumor microenvironment. Evidence has shown differences in the functions and fates of MDSCs in the tumor tissue and the periphery. However, the exact mechanism that regulates MDSC function has not been completely clarified. In this study, we performed RNA sequencing of MDSCs derived from the spleen and tumor. Based on the results of our RNA-seq analysis, mitogen-activated protein kinases (MAPK) were significantly increased in tumor polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs). Subsequently, 3 major MAPK pathways, including extracellular signal-regulated protein kinases (ERK), p38 and c-Jun NH2-terminal kinases (JNK), were studied to analyze the role of MAPKs in MDSCs. The ERK 1/2 inhibitor SCH772984 and the JNK inhibitor SP600125 significantly increased the apoptosis of both PMN-MDSCs and M-MDSCs in vitro. In addition, SCH772984 exerted a strong effect on inhibiting tumor growth. The flow cytometry analysis showed significant increases in the ratio of M1:M2 tumor-associated macrophages, meanwhile the number of CD4+, CD8+, CD4+CD69+ and CD8+CD69+ lymphocytes were increased after SCH772984 treatment. Our findings established the effect of MAPKs on the tumor microenvironment via MDSCs and may facilitate the development of new antitumor strategies.

scholarly journals How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer

2021 ◽  
Author(s):  
Jacob Stultz ◽  
Lawrence Fong
Keyword(s):  
Prostate Cancer ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Treatment Options ◽  
Suppressor Cells ◽  
Prostatic Acid Phosphatase ◽  
Clinical Activity ◽  
Immune Resistance ◽  
Tumor Growth Factor ◽  
The Impact

Abstract Background Advanced prostate cancer remains one of the most common and deadly cancers, despite advances in treatment options. Immunotherapy has provided little benefit to a majority of patients, largely due to the immunosuppressive tumor microenvironment that gives rise to inherently “cold tumors”. In this review, we discuss the immunopathology of the prostate tumor microenvironment, strategies for treating prostate cancer with immunotherapies, and a perspective on potential approaches to enhancing the efficacy of immunotherapies. Methods Databases, including PubMed, Google Scholar, and Cochrane, were searched for articles relevant to the immunology of prostate cancer. We discuss the impact of different types of treatments on the immune system, and potential mechanisms through which prostate cancer evades the immune system. Results The tumor microenvironment associated with prostate cancer is highly immunosuppressive due to (1) the function of regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSCs), (2) the cytokine milieu secreted by tumor stromal cells and fibroblasts, and (3) the production of adenosine via prostatic acid phosphatase. Both adenosine and tumor growth factor beta (TGF-beta) serve as potent immunosuppressive molecules that could also represent potential therapeutic targets. While there have been many immunotherapy trials in prostate cancer, the majority of these trials have targeted a single immunosuppressive mechanism resulting in limited clinical efficacy. Future approaches will require the integration of improved patient selection as well as use of combination therapies to address multiple mechanisms of resistance. Conclusion Prostate cancer inherently gives rise to multiple immunosuppressive mechanisms that have been difficult to overcome with any one immunotherapeutic approach. Enhancing the clinical activity of immunotherapies will require strategic combinations of multiple therapies to address the emerging mechanisms of tumor immune resistance.

In situ TEM studies of irradiation effects for materials improvement

1991 ◽  
Vol 49 ◽  
pp. 452-453
Author(s):  
Charles W. Allen
Keyword(s):  
Nuclear Reactor ◽  
Austenitic Stainless Steels ◽  
High Energy ◽  
Point Of View ◽  
In Situ Tem ◽  
Irradiation Effects ◽  
Tem Analysis ◽  
Radiation Induced ◽  
Analytical Tools

Irradiation effects studies employing TEMs as analytical tools have been conducted for almost as many years as materials people have done TEM, motivated largely by materials needs for nuclear reactor development. Such studies have focussed on the behavior both of nuclear fuels and of materials for other reactor components which are subjected to radiation-induced degradation. Especially in the 1950s and 60s, post-irradiation TEM analysis may have been coupled to in situ (in reactor or in pile) experiments (e.g., irradiation-induced creep experiments of austenitic stainless steels). Although necessary from a technological point of view, such experiments are difficult to instrument (measure strain dynamically, e.g.) and control (temperature, e.g.) and require months or even years to perform in a nuclear reactor or in a spallation neutron source. Consequently, methods were sought for simulation of neutroninduced radiation damage of materials, the simulations employing other forms of radiation; in the case of metals and alloys, high energy electrons and high energy ions.

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