Autophagy in the Immunosuppressive Perivascular Microenvironment of Glioblastoma

Glioblastoma (GB) has been shown to up-regulate autophagy with anti- or pro-oncogenic effects. Recently, our group has shown how GB cells aberrantly up-regulate chaperone-mediated autophagy (CMA) in pericytes of peritumoral areas to modulate their immune function through cell-cell interaction and in the tumor’s own benefit. Thus, to understand GB progression, the effect that GB cells could have on autophagy of immune cells that surround the tumor needs to be deeply explored. In this review, we summarize all the latest evidence of several molecular and cellular immunosuppressive mechanisms in the perivascular tumor microenvironment. This immunosuppression has been reported to facilitate GB progression and may be differently modulated by several types of autophagy as a critical point to be considered for therapeutic interventions.

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Mesenchymal Stem Cells and Cancer Stem Cells: An Overview of Tumor-Mesenchymal Stem Cell Interaction for therapeutic interventions

Current Drug Targets ◽

10.2174/1389450122666210824142247 ◽

2021 ◽

Vol 22 ◽

Author(s):

Soheila Montazersaheb ◽

Ezzatollah Fathi ◽

Ayoub Mamandi ◽

Raheleh Farahzadi ◽

Hamid Reza Heidari

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tumor Microenvironment ◽

Cancer Stem Cells ◽

Tumor Cells ◽

Cell Types ◽

Cell Interaction ◽

Therapeutic Interventions ◽

Tumorigenic Potential ◽

Different Types

: Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.

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Correlation between MDSC and Immune Tolerance in Transplantation: Cytokines, Pathways and Cell-cell Interaction

Current Gene Therapy ◽

10.2174/1566523219666190618093707 ◽

2019 ◽

Vol 19 (2) ◽

pp. 81-92 ◽

Cited By ~ 2

Author(s):

Tianying Yang ◽

Jiawei Li ◽

Ruimin Li ◽

Chunchen Yang ◽

Weitao Zhang ◽

...

Keyword(s):

Signaling Pathways ◽

Graft Survival ◽

Immune Tolerance ◽

Immune Cells ◽

Cell Interaction ◽

Erk Signaling ◽

Gm Csf ◽

Cytokines And Chemokines ◽

Direct Suppression ◽

Cell Cell

MDSCs play an important role in the induction of immune tolerance. Cytokines and chemokines (GM-CSF, IL-6) contributed to the expansion, accumulation of MDSCs, and MDSCs function through iNOS, arginase and PD-L1. MDSCs are recruited and regulated through JAK/STAT, mTOR and Raf/MEK/ERK signaling pathways. MDSCs’ immunosuppressive functions were realized through Tregs-mediated pathways and their direct suppression of immune cells. All of the above contribute to the MDSC-related immune tolerance in transplantation. MDSCs have huge potential in prolonging graft survival and reducing rejection through different ways and many other factors worthy to be further investigated are also introduced.

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Agent-Based Learning Model for the Obesity Paradox in RCC

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.642760 ◽

2021 ◽

Vol 9 ◽

Author(s):

Matteo Belenchia ◽

Giacomo Rocchetti ◽

Stefano Maestri ◽

Alessia Cimadamore ◽

Rodolfo Montironi ◽

...

Keyword(s):

Tumor Microenvironment ◽

Environmental Changes ◽

Interaction Network ◽

Obesity Paradox ◽

Cell Interaction ◽

Computational Framework ◽

Agent Based ◽

Medical Needs ◽

Starting Model ◽

Cell Cell

A recent study on the immunotherapy treatment of renal cell carcinoma reveals better outcomes in obese patients compared to lean subjects. This enigmatic contradiction has been explained, in the context of the debated obesity paradox, as the effect produced by the cell-cell interaction network on the tumor microenvironment during the immune response. To better understand this hypothesis, we provide a computational framework for the in silico study of the tumor behavior. The starting model of the tumor, based on the cell-cell interaction network, has been described as a multiagent system, whose simulation generates the hypothesized effects on the tumor microenvironment. The medical needs in the immunotherapy design meet the capabilities of a multiagent simulator to reproduce the dynamics of the cell-cell interaction network, meaning a reaction to environmental changes introduced through the experimental data.

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Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00825-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Wen Li ◽

Feifei Li ◽

Xia Zhang ◽

Huikuan Lin ◽

Chuan Xu

Keyword(s):

Tumor Microenvironment ◽

Cancer Progression ◽

Immune Cells ◽

Tumor Heterogeneity ◽

Dynamic Change ◽

Therapeutic Interventions ◽

Post Translational Modification ◽

Recent Developments ◽

Physiological Homeostasis ◽

Tumor Infiltrate

AbstractMore and more in-depth studies have revealed that the occurrence and development of tumors depend on gene mutation and tumor heterogeneity. The most important manifestation of tumor heterogeneity is the dynamic change of tumor microenvironment (TME) heterogeneity. This depends not only on the tumor cells themselves in the microenvironment where the infiltrating immune cells and matrix together forming an antitumor and/or pro-tumor network. TME has resulted in novel therapeutic interventions as a place beyond tumor beds. The malignant cancer cells, tumor infiltrate immune cells, angiogenic vascular cells, lymphatic endothelial cells, cancer-associated fibroblastic cells, and the released factors including intracellular metabolites, hormonal signals and inflammatory mediators all contribute actively to cancer progression. Protein post-translational modification (PTM) is often regarded as a degradative mechanism in protein destruction or turnover to maintain physiological homeostasis. Advances in quantitative transcriptomics, proteomics, and nuclease-based gene editing are now paving the global ways for exploring PTMs. In this review, we focus on recent developments in the PTM area and speculate on their importance as a critical functional readout for the regulation of TME. A wealth of information has been emerging to prove useful in the search for conventional therapies and the development of global therapeutic strategies.

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Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity

Frontiers in Oncology ◽

10.3389/fonc.2021.782043 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zujian Xiong ◽

Hongwei Liu ◽

Chenqi He ◽

Xuejun Li

Keyword(s):

Gene Expression ◽

Tumor Microenvironment ◽

Tumor Cell ◽

Tumor Cells ◽

Immune Cells ◽

Cell Activity ◽

Cell Communication ◽

Gene Set Enrichment Analysis ◽

Rna Seq ◽

Cell Cell

AimsTo reveal the influence of hypoxia on tumor cells and immune cells in primary IDH-wt glioblastoma patients.MethodsSingle-cell RNA-seq data and bulk RNA-seq data were acquired from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. Hypoxia status and subtypes of tumor cells were identified based on single-sample Gene Set Enrichment Analysis (ssGSEA). Regulon network analysis of different subtypes under different conditions was conducted by SCENIC. Within tumor microenvironment, biological process activity analysis and cell–cell communication network were conducted to uncover the inner links between each cell subtype under different hypoxia status.ResultsDifferent types of tumor cell in GBM possessed different hypoxia status, and MES-like subtype was under a more severe hypoxia condition than other subtypes. Hypoxia also induced MES-like signature gene expression within each tumor cell, which could stimulate tumor cell proliferation and invasion by regulating cell–cell communication. Additionally, hypoxia inhibited immune cell activity in the tumor microenvironment by inducing macrophage phenotype polarization and upregulating immune-inhibited cell–cell interaction within immune cells. Interactions between tumor cells and immune cells under hypoxia status also promoted tumor progression.ConclusionsHypoxia was a poor prognostic marker for primary IDH-wt GBM patients. Meanwhile, it could induce tumor cells’ MES-like transformation trend and inhibit antitumor function of immune cells.

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Cross Talk of Macrophages with Tumor Microenvironment Cells and Modulation of Macrophages in Cancer by Virotherapy

Biomedicines ◽

10.3390/biomedicines9101309 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1309

Author(s):

Sarah Di Somma ◽

Fabiana Napolitano ◽

Giuseppe Portella ◽

Anna Maria Malfitano

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tumor Microenvironment ◽

Immune Cells ◽

Tumor Response ◽

Cell Interaction ◽

Oncolytic Viruses ◽

Malignant Cells ◽

Cellular Compartments ◽

Stromal Stem Cells

Cellular compartments constituting the tumor microenvironment including immune cells, fibroblasts, endothelial cells, and mesenchymal stromal/stem cells communicate with malignant cells to orchestrate a series of signals that contribute to the evolution of the tumor microenvironment. In this study, we will focus on the interplay in tumor microenvironment between macrophages and mesenchymal stem cells and macrophages and fibroblasts. In particular, cell–cell interaction and mediators secreted by these cells will be examined to explain pro/anti-tumor phenotypes induced in macrophages. Nonetheless, in the context of virotherapy, the response of macrophages as a consequence of treatment with oncolytic viruses will be analyzed regarding their polarization status and their pro/anti-tumor response.

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3560 Essential role of cell-cell interaction via Mac-1 and ICAM-1 during arteriogenesis

European Heart Journal ◽

10.1016/s0195-668x(03)96158-6 ◽

2003 ◽

Vol 24 (5) ◽

pp. 692

Author(s):

J HUA

Keyword(s):

Essential Role ◽

Cell Interaction ◽

Cell Cell

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ROS-responsive nanomedicine: Towards targeting the breast tumor microenvironment

Current Medicinal Chemistry ◽

10.2174/0929867328666201209100659 ◽

2020 ◽

Vol 28 ◽

Author(s):

RamaRao Malla ◽

Mohammad Amjad Kamal

Keyword(s):

Reactive Oxygen Species ◽

Gene Therapy ◽

Drug Resistance ◽

Molecular Imaging ◽

Tumor Microenvironment ◽

Immune Cells ◽

Breast Tumor ◽

Imaging Techniques ◽

Oxygen Species ◽

Massive Accumulation

: The breast tumor microenvironment (TME) promotes drug resistance through an elaborated interaction of TME components mediated by reactive oxygen species (ROS). Despite a massive accumulation of data concerning the targeting the ROS, but little is known about the ROS-responsive nanomedicine for targeting breast TME. This review submits the ROS landscape in breast TME, including ROS biology, ROS mediated carcinogenesis, reprogramming of stromal and immune cells of TME. We also discussed ROS-based precision strategies for imaging TME, including molecular imaging techniques with advanced probes, multiplexed methods, and multi-omic profiling strategies. ROS-responsive nanomedicine also describes various therapies, such as chemo-dynamic, photodynamic, photothermal, sono-dynamic, immune, and gene therapy for BC. We expound ROS-responsive primary delivery systems for chemotherapeutics, phytochemicals, and immunotherapeutics. This review also presents recent updates on nano-theranostics for simultaneous diagnosis and treatment of BCs. We assume that review on this advancing field will be beneficial to the development of ROS-based nanotheranostics for BC.

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