scholarly journals Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tiecheng Wang ◽  
Jiakang Jin ◽  
Chao Qian ◽  
Jianan Lou ◽  
Jinti Lin ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Target Genes ◽  
Target Therapy ◽  
Treatment Strategies ◽  
Signal Transduction Pathway ◽  
Pathway Activation ◽  
Immune System Regulation

AbstractAs the essential sexual hormone, estrogen and its receptor has been proved to participate in the regulation of autoimmunity diseases and anti-tumor immunity. The adjustment of tumor immunity is related to the interaction between cancer cells, immune cells and tumor microenvironment, all of which is considered as the potential target in estrogen-induced immune system regulation. However, the specific mechanism of estrogen-induced immunity is poorly understood. Typically, estrogen causes the nuclear localization of estrogen/estrogen receptor complex and alternates the transcription pattern of target genes, leading to the reprogramming of tumor cells and differentiation of immune cells. However, the estrogen-induced non-canonical signal pathway activation is also crucial to the rapid function of estrogen, such as NF-κB, MAPK-ERK, and β-catenin pathway activation, which has not been totally illuminated. So, the investigation of estrogen modulatory mechanisms in these two manners is vital for the tumor immunity and can provide the potential for endocrine hormone targeted cancer immunotherapy. Here, this review summarized the estrogen-induced canonical and non-canonical signal transduction pathway and aimed to focus on the relationship among estrogen and cancer immunity as well as immune-related tumor microenvironment regulation. Results from these preclinical researches elucidated that the estrogen-target therapy has the application prospect of cancer immunotherapy, which requires the further translational research of these treatment strategies.

scholarly journals When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Katrin Schlie ◽  
Jaeline E. Spowart ◽  
Luke R. K. Hughson ◽  
Katelin N. Townsend ◽  
Julian J. Lum
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Patient Treatment ◽  
Low Oxygen ◽  
Tumor Environment ◽  
And Function ◽  
The Impact

Hypoxia is a signature feature of growing tumors. This cellular state creates an inhospitable condition that impedes the growth and function of all cells within the immediate and surrounding tumor microenvironment. To adapt to hypoxia, cells activate autophagy and undergo a metabolic shift increasing the cellular dependency on anaerobic metabolism. Autophagy upregulation in cancer cells liberates nutrients, decreases the buildup of reactive oxygen species, and aids in the clearance of misfolded proteins. Together, these features impart a survival advantage for cancer cells in the tumor microenvironment. This observation has led to intense research efforts focused on developing autophagy-modulating drugs for cancer patient treatment. However, other cells that infiltrate the tumor environment such as immune cells also encounter hypoxia likely resulting in hypoxia-induced autophagy. In light of the fact that autophagy is crucial for immune cell proliferation as well as their effector functions such as antigen presentation and T cell-mediated killing of tumor cells, anticancer treatment strategies based on autophagy modulation will need to consider the impact of autophagy on the immune system.

scholarly journals The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengguo Wu ◽  
Shang Li ◽  
Xiao Zhu
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Checkpoint Inhibitors ◽  
The Body ◽  
Research Progress ◽  
Effective Population ◽  
Cell Components

Cancer immunotherapy is a kind of therapy that can control and eliminate tumors by restarting and maintaining the tumor-immune cycle and restoring the body’s normal anti-tumor immune response. Although immunotherapy has great potential, it is currently only applicable to patients with certain types of tumors, such as melanoma, lung cancer, and cancer with high mutation load and microsatellite instability, and even in these types of tumors, immunotherapy is not effective for all patients. In order to enhance the effectiveness of tumor immunotherapy, this article reviews the research progress of tumor microenvironment immunotherapy, and studies the mechanism of stimulating and mobilizing immune system to enhance anti-tumor immunity. In this review, we focused on immunotherapy against tumor microenvironment (TME) and discussed the important research progress. TME is the environment for the survival and development of tumor cells, which is composed of cell components and non-cell components; immunotherapy for TME by stimulating or mobilizing the immune system of the body, enhancing the anti-tumor immunity. The checkpoint inhibitors can effectively block the inhibitory immunoregulation, indirectly strengthen the anti-tumor immune response and improve the effect of immunotherapy. We also found the checkpoint inhibitors have brought great changes to the treatment model of advanced tumors, but the clinical treatment results show great individual differences. Based on the close attention to the future development trend of immunotherapy, this study summarized the latest progress of immunotherapy and pointed out a new direction. To study the mechanism of stimulating and mobilizing the immune system to enhance anti-tumor immunity can provide new opportunities for cancer treatment, expand the clinical application scope and effective population of cancer immunotherapy, and improve the survival rate of cancer patients.

scholarly journals In Vivo CRISPR Screens Identify E3 Ligase Cop1 as a Modulator of Macrophage Infiltration and Cancer Immunotherapy Target

2020 ◽  
Author(s):  
Xiaoqing Wang ◽  
Collin Tokheim ◽  
Binbin Wang ◽  
Shengqing Stan Gu ◽  
Qin Tang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Large Scale ◽  
Integrated Approach ◽  
Immune Checkpoint Blockade ◽  
Macrophage Infiltration ◽  
List Type

SUMMARYDespite remarkable clinical efficacies of immune checkpoint blockade (ICB) in cancer treatment, ICB benefits in triple-negative breast cancer (TNBC) remain limited. Through pooled in vivo CRISPR knockout (KO) screens in syngeneic TNBC mouse models, we found that inhibition of the E3 ubiquitin ligase Cop1 in cancer cells decreases the secretion of macrophage-associated chemokines, reduces tumor macrophage infiltration, and shows synergy in anti-tumor immunity with ICB. Transcriptomics, epigenomics, and proteomics analyses revealed Cop1 functions through proteasomal degradation of the C/ebpδ protein. Cop1 substrate Trib2 functions as a scaffold linking Cop1 and C/ebpδ, which leads to polyubiquitination of C/ebpδ. Cop1 inhibition stabilizes C/ebpδ to suppress the expression of macrophage chemoattractant genes. Our integrated approach implicates Cop1 as a target for improving cancer immunotherapy efficacy by regulating chemokine secretion and macrophage levels in the TNBC tumor microenvironment.HighlightsLarge-scale in vivo CRISPR screens identify new immune targets regulating the tumor microenvironmentCop1 knockout in cancer cells enhances anti-tumor immunityCop1 modulates chemokine secretion and macrophage infiltration into tumorsCop1 targets C/ebpδ degradation via Trib2 and influences ICB response

scholarly journals Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ming Jia ◽  
Dan Zhang ◽  
Chunxiang Zhang ◽  
Chunhong Li
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Malignant Tumors ◽  
Treatment Strategies ◽  
Delivery Systems ◽  
Cancer Microenvironment ◽  
Cancer Associated Fibroblasts ◽  
Hypoxic Environment ◽  
Promising Therapeutic Approach

AbstractPancreatic cancer is one of the most lethal malignant tumors with a low survival rate, partly because the tumor microenvironment (TME), which consists of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), immune cells, and vascular systems, prevents effective drug delivery and chemoradiotherapy. Thus, modulating the microenvironment of pancreatic cancer is considered a promising therapeutic approach. Since nanoparticles are one of the most effective cancer treatment strategies, several nano-delivery platforms have been developed to regulate the TME and enhance treatment. Here, we summarize the latest advances in nano-delivery systems that alter the TME in pancreatic cancer by depleting ECM, inhibiting CAFs, reversing immunosuppression, promoting angiogenesis, or improving the hypoxic environment. We also discuss promising new targets for such systems. This review is expected to improve our understanding of how to modulate the pancreatic cancer microenvironment and guide the development of new therapies. Graphical Abstract

scholarly journals Indoleamine 2,3-dioxygenase regulates anti-tumor immunity in lung cancer by metabolic reprogramming of immune cells in the tumor microenvironment

Oncotarget ◽  
2016 ◽  
Vol 7 (46) ◽  
pp. 75407-75424 ◽  
Author(s):  
Cara C. Schafer ◽  
Yong Wang ◽  
Kenneth P. Hough ◽  
Anandi Sawant ◽  
Stefan C. Grant ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Metabolic Reprogramming ◽  
Indoleamine 2,3 Dioxygenase

scholarly journals MicroRNAs: immune modulators in cancer immunotherapy

2021 ◽  
Author(s):  
Yun Xing ◽  
Zhiqiang Wang ◽  
Zhou Lu ◽  
Jie Xia ◽  
Zhangjuan Xie ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Tumor Suppressors ◽  
Immune Modulators ◽  
Non Coding Rna ◽  
New Findings

Abstract MicroRNA (miRNA) is a class of endogenous small non-coding RNA of 18–25 nucleotides and plays regulatory roles in both physiological and pathological processes. Emerging evidence support that miRNAs function as immune modulators in tumors. MiRNAs as tumor suppressors or oncogenes are also found to be able to modulate anti-tumor immunity or link the crosstalk between tumor cells and immune cells surrounding. Based on the specific regulating function, miRNAs can be used as predictive, prognostic biomarkers and therapeutic targets in immunotherapy. Here, we review new findings about role of miRNAs in modulating immune responses, as well as discuss mechanisms underlying their dysregulation, and their clinical potentials as indicators of tumor prognosis or to sensitize cancer immunotherapy.

scholarly journals Phosphorylation of SMAD3 in immune cells predicts survival of patients with early stage non-small cell lung cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001469
Author(s):  
Sebastian Marwitz ◽  
Carmen Ballesteros-Merino ◽  
Shawn M Jensen ◽  
Martin Reck ◽  
Christian Kugler ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Pathway Activation ◽  
Smad3 Phosphorylation

BackgroundThe interplay of immune and cancer cells takes place in the tumor microenvironment where multiple signals are exchanged. The transforming growth factor beta (TGFB) pathway is known to be dysregulated in lung cancer and can impede an effective immune response. However, the exact mechanisms are yet to be determined. Especially which cells respond and where does this signaling take place with respect to the local microenvironment.MethodsHuman non-small cell lung cancer samples were retrospectively analyzed by multiplexed immunohistochemistry for SMAD3 phosphorylation and programmed death ligand 1 expression in different immune cells with respect to their localization within the tumor tissue. Spatial relationships were studied to examine possible cell-cell interactions and analyzed in conjunction with clinical data.ResultsTGFB pathway activation in CD3, CD8, Foxp3 and CD68 cells, as indicated by SMAD3 phosphorylation, negatively impacts overall and partially disease-free survival of patients with lung cancerindependent of histological subtype. A high frequency of Foxp3 regulatory T cells positive for SMAD3 phosphorylation in close vicinity of CD8 T cells within the tumor discriminate a rapidly progressing group of patients with lung cancer.ConclusionsTGFB pathway activation of local immune cells within the tumor microenvironment impacts survival of early stage lung cancer. This might benefit patients not eligible for targeted therapies or immune checkpoint therapy as a therapeutic option to re-activate the local immune response.

scholarly journals Therapeutic Targeting of MicroRNAs in the Tumor Microenvironment

2021 ◽  
Vol 22 (4) ◽  
pp. 2210 ◽  
Author(s):  
Rebecca Raue ◽  
Ann-Christin Frank ◽  
Shahzad Nawaz Syed ◽  
Bernhard Brüne
Keyword(s):  
Tumor Microenvironment ◽  
Target Genes ◽  
Tumor Therapy ◽  
Treatment Strategies ◽  
Salient Feature ◽  
Host Cells ◽  
Transcriptional Level ◽  
Preclinical Trials ◽  
Almost All ◽  
Cell Phenotypes

The tumor-microenvironment (TME) is an amalgamation of various factors derived from malignant cells and infiltrating host cells, including cells of the immune system. One of the important factors of the TME is microRNAs (miRs) that regulate target gene expression at a post transcriptional level. MiRs have been found to be dysregulated in tumor as well as in stromal cells and they emerged as important regulators of tumorigenesis. In fact, miRs regulate almost all hallmarks of cancer, thus making them attractive tools and targets for novel anti-tumoral treatment strategies. Tumor to stroma cell cross-propagation of miRs to regulate protumoral functions has been a salient feature of the TME. MiRs can either act as tumor suppressors or oncogenes (oncomiRs) and both miR mimics as well as miR inhibitors (antimiRs) have been used in preclinical trials to alter cancer and stromal cell phenotypes. Owing to their cascading ability to regulate upstream target genes and their chemical nature, which allows specific pharmacological targeting, miRs are attractive targets for anti-tumor therapy. In this review, we cover a recent update on our understanding of dysregulated miRs in the TME and provide an overview of how these miRs are involved in current cancer-therapeutic approaches from bench to bedside.

scholarly journals Mesenchymal Stem Cell: A Friend or Foe in Anti-Tumor Immunity

2021 ◽  
Vol 22 (22) ◽  
pp. 12429
Author(s):  
Carl Randall Harrell ◽  
Ana Volarevic ◽  
Valentin G. Djonov ◽  
Nemanja Jovicic ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Cellular Mechanisms ◽  
Multipotent Stem Cells ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, multipotent stem cells that regulate the phenotype and function of all immune cells that participate in anti-tumor immunity. MSCs modulate the antigen-presenting properties of dendritic cells, affect chemokine and cytokine production in macrophages and CD4+ T helper cells, alter the cytotoxicity of CD8+ T lymphocytes and natural killer cells and regulate the generation and expansion of myeloid-derived suppressor cells and T regulatory cells. As plastic cells, MSCs adopt their phenotype and function according to the cytokine profile of neighboring tumor-infiltrated immune cells. Depending on the tumor microenvironment to which they are exposed, MSCs may obtain pro- and anti-tumorigenic phenotypes and may enhance or suppress tumor growth. Due to their tumor-homing properties, MSCs and their exosomes may be used as vehicles for delivering anti-tumorigenic agents in tumor cells, attenuating their viability and invasive characteristics. Since many factors affect the phenotype and function of MSCs in the tumor microenvironment, a better understanding of signaling pathways that regulate the cross-talk between MSCs, immune cells and tumor cells will pave the way for the clinical use of MSCs in cancer immunotherapy. In this review article, we summarize current knowledge on the molecular and cellular mechanisms that are responsible for the MSC-dependent modulation of the anti-tumor immune response and we discuss different insights regarding therapeutic potential of MSCs in the therapy of malignant diseases.

scholarly journals The CC and CXC chemokines: major regulators of tumor progression and the tumor microenvironment

2020 ◽  
Vol 318 (3) ◽  
pp. C542-C554 ◽  
Author(s):  
Andreas Bikfalvi ◽  
Clotilde Billottet
Keyword(s):  
Cell Proliferation ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Chemokine Receptor ◽  
Immune Cells ◽  
Immune Dysfunction ◽  
Mechanisms Of Action ◽  
Migration Of Cells

Chemokines are a family of soluble cytokines that act as chemoattractants to guide the migration of cells, in particular of immune cells. However, chemokines are also involved in cell proliferation, differentiation, and survival. Chemokines are associated with a variety of human diseases including chronic inflammation, immune dysfunction, cancer, and metastasis. This review discusses the expression of CC and CXC chemokines in the tumor microenvironment and their supportive and inhibitory roles in tumor progression, angiogenesis, metastasis, and tumor immunity. We also specially focus on the diverse roles of CXC chemokines (CXCL9–11, CXCL4 and its variant CXCL4L1) and their two chemokine receptor CXCR3 isoforms, CXCR3-A and CXCR3-B. These two distinct isoforms have divergent roles in tumors, either promoting (CXCR3-A) or inhibiting (CXCR3-B) tumor progression. Their effects are mediated not only directly in tumor cells but also indirectly via the regulation of angiogenesis and tumor immunity. A full comprehension of their mechanisms of action is critical to further validate these chemokines and their receptors as biomarkers or therapeutic targets in cancer.

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