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

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.

scholarly journals Metabolic Reprogramming Induces Immune Cell Dysfunction in the Tumor Microenvironment of Multiple Myeloma

2021 ◽  
Vol 10 ◽  
Author(s):  
Shaojie Wu ◽  
Huixian Kuang ◽  
Jin Ke ◽  
Manfei Pi ◽  
Dong-Hua Yang
Keyword(s):  
Multiple Myeloma ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Cell Dysfunction ◽  
Promising Therapeutic Approach ◽  
Tumor Survival

Tumor cells rewire metabolism to meet their increased nutritional demands, allowing the maintenance of tumor survival, proliferation, and expansion. Enhancement of glycolysis and glutaminolysis is identified in most, if not all cancers, including multiple myeloma (MM), which interacts with a hypoxic, acidic, and nutritionally deficient tumor microenvironment (TME). In this review, we discuss the metabolic changes including generation, depletion or accumulation of metabolites and signaling pathways, as well as their relationship with the TME in MM cells. Moreover, we describe the crosstalk among metabolism, TME, and changing function of immune cells during cancer progression. The overlapping metabolic phenotype between MM and immune cells is discussed. In this sense, targeting metabolism of MM cells is a promising therapeutic approach. We propose that it is important to define the metabolic signatures that may regulate the function of immune cells in TME in order to improve the response to immunotherapy.

scholarly journals Targeting the Tumor Microenvironment for Cancer Therapy

2013 ◽  
Vol 59 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Nor Eddine Sounni ◽  
Agnès Noel
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Local Environment ◽  
Tumor Stroma ◽  
Host Cells ◽  
Stromal Compartment ◽  
Tumor Infiltrate ◽  
Cellular Components

BACKGROUND With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in the clinic. CONTENT The malignant features of cancer cells cannot be manifested without an important interplay between cancer cells and their local environment. The tumor infiltrate composed of immune cells, angiogenic vascular cells, lymphatic endothelial cells, and cancer-associated fibroblastic cells contributes actively to cancer progression. The ability to change these surroundings is an important property by which tumor cells are able to acquire some of the hallmark functions necessary for tumor growth and metastatic dissemination. Thus in the clinical setting the targeting of the tumor microenvironment to encapsulate or destroy cancer cells in their local environment has become mandatory. The variety of stromal cells, the complexity of the molecular components of the tumor stroma, and the similarity with normal tissue present huge challenges for therapies targeting the tumor microenvironment. These issues and their interplay are addressed in this review. After a decade of intensive clinical trials targeting cellular components of the tumor microenvironment, more recent investigations have shed light on the important role in cancer progression played by the noncellular stromal compartment composed of the extracellular matrix. SUMMARY A better understanding of how the tumor environment affects cancer progression should provide new targets for the isolation and destruction of cancer cells via interference with the complex crosstalk established between cancer cells, host cells, and their surrounding extracellular matrix.

scholarly journals The Crosstalk between Ovarian Cancer Stem Cell Niche and the Tumor Microenvironment

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Manuel Varas-Godoy ◽  
Gregory Rice ◽  
Sebastián E. Illanes
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Stem Cell Niche ◽  
Small Population ◽  
The World ◽  
Cell Niche

Ovarian cancer is one of the most important causes of cancer-related death among women in the world. Despite advances in ovarian cancer treatment, 70–80% of women who initially respond to therapy eventually relapse and die. There is evidence that a small population of cells within the tumors called cancer stem cells (CSCs) could be responsible for treatment failure due to their enhanced chemoresistance and tumorigenicity. These cells reside in a niche that maintains the principal properties of CSCs. These properties are associated with the capacity of CSCs to interact with different cells of the tumor microenvironment including mesenchymal stem cells, endothelial cells, immune cells, and fibroblasts, promoting cancer progression. This interaction can be mediated by cytokines, growth factors, lipids, and/or extracellular vesicles released in the CSC niche. In this review, we will discuss how the interaction between ovarian CSCs and the tumor microenvironment can contribute to the maintenance of the CSC niche and consequently to tumor progression in ovarian cancer.

MUC glycoproteins: Potential biomarkers and molecular targets for cancer therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Chameli Ratan ◽  
Dalia Cicily K. D ◽  
Bhagyalakshmi Nair ◽  
Lekshmi R. Nath
Keyword(s):  
Cancer Therapy ◽  
Cancer Progression ◽  
Wide Spectrum ◽  
Primary Liver Cancer ◽  
Structural Complexity ◽  
Biochemical Properties ◽  
Therapeutic Interventions ◽  
Post Translational Modification ◽  
Cancer Cell Growth ◽  
Aberrant Expression

: MUC proteins have great significance as prognostic and diagnostic markers as well as a potential target for therapeutic interventions in most cancers of glandular epithelial origin. These are high molecular weight glycosylated proteins located in the epithelial lining of several tissues and ducts. Mucins belong to a heterogeneous group of large O-glycoproteins that can be either secreted or membrane-bound. Glycosylation, a post-translational modification affects the bio-physical, functional and biochemical properties and provides structural complexity for these proteins. Aberrant expression and glycosylation of mucins contribute to tumour survival and proliferation in many cancers, which in turn activates numerous signalling pathways such as NF-kB, ERα, HIF, MAPK, p53, c-Src, Wnt and JAK-STAT etc. This subsequently induces cancer cell growth, proliferation and metastasis. The present review mainly demonstrates the functional aspects of MUC glycoproteins along with its unique signalling mechanism and role of aberrant glycosylation in cancer progression and therapeutics. The importance of MUC proteins and its subtypes in a wide spectrum of cancers including but not limited to breast cancer, colorectal cancer, endometrial and cervical cancer, lung cancer, primary liver cancer, pancreatic cancer, prostate cancer and ovarian cancer have been exemplified with its significance in targeting the same. Several patents associated with the MUC proteins in the field of cancer therapy are also emphasized in the current review.

Extracellular vesicles in cancer progression: are they part of the problem or part of the solution?

Nanomedicine ◽  
2020 ◽  
Vol 15 (26) ◽  
pp. 2625-2641
Author(s):  
Juliete Nathali Scholl ◽  
Camila Kehl Dias ◽  
Laurent Muller ◽  
Ana Maria Oliveira Battastini ◽  
Fabrício Figueiró
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cell Function ◽  
Cytokine Release

Extracellular vesicles (EVs) are released especially by cancer cells. They modulate the tumor microenvironment by interacting with immune cells while carrying immunosuppressive or immunostimulatory molecules. In this review, we will explore some conflicting reports regarding the immunological outcomes of EVs in cancer progression, in which they might initiate an antitumor immune response or an immunosuppressive response. Concerning immunosuppression, the role of tumor-derived EVs’ in the adenosinergic system is underexplored. The enhancement of adenosine (ADO) levels in the tumor microenvironment impairs T-cell function and cytokine release. However, some tumor-derived EVs may deliver immunostimulatory factors, promoting immunogenic activity, even with ADO production. The modulatory role of ADO over the tumor progression represents a piece in an intricate microenvironment with anti and pro tumoral seesaw-like mechanisms.

scholarly journals Senescence in the Development and Response to Cancer with Immunotherapy: A Double-Edged Sword

2020 ◽  
Vol 21 (12) ◽  
pp. 4346 ◽  
Author(s):  
Anthony M. Battram ◽  
Mireia Bachiller ◽  
Beatriz Martín-Antonio
Keyword(s):  
Tumor Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Cell ◽  
Tumor Development ◽  
Cell Senescence ◽  
Therapeutic Interventions ◽  
Main Role ◽  
Suppressor Mechanism

Cellular senescence was first described as a physiological tumor cell suppressor mechanism that leads to cell growth arrest with production of the senescence-associated secretory phenotype known as SASP. The main role of SASP in physiological conditions is to attract immune cells to clear senescent cells avoiding tumor development. However, senescence can be damage-associated and, depending on the nature of these stimuli, additional types of senescence have been described. In the context of cancer, damage-associated senescence has been described as a consequence of chemotherapy treatments that were initially thought of as a tumor suppressor mechanism. However, in certain contexts, senescence after chemotherapy can promote cancer progression, especially when immune cells become senescent and cannot clear senescent tumor cells. Moreover, aging itself leads to continuous inflammaging and immunosenescence which are responsible for rewiring immune cells to become defective in their functionality. Here, we define different types of senescence, pathways that activate them, and functions of SASP in these events. Additionally, we describe the role of senescence in cancer and its treatments, including how aging and chemotherapy contribute to senescence in tumor cells, before focusing on immune cell senescence and its role in cancer. Finally, we discuss potential therapeutic interventions to reverse cell senescence.

scholarly journals A Holistic Perspective: Exosomes Shuttle between Nerves and Immune Cells in the Tumor Microenvironment

2020 ◽  
Vol 9 (11) ◽  
pp. 3529
Author(s):  
Mihnea P. Dragomir ◽  
Vlad Moisoiu ◽  
Roxana Manaila ◽  
Barbara Pardini ◽  
Erik Knutsen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Checkpoint Inhibitors ◽  
Systemic Disease ◽  
Improved Outcomes ◽  
Complex Landscape ◽  
Endothelial Growth Factor

One of the limitations of cancer research has been the restricted focus on tumor cells and the omission of other non-malignant cells that are constitutive elements of this systemic disease. Current research is focused on the bidirectional communication between tumor cells and other components of the tumor microenvironment (TME), such as immune and endothelial cells, and nerves. A major success of this bidirectional approach has been the development of immunotherapy. Recently, a more complex landscape involving a multi-lateral communication between the non-malignant components of the TME started to emerge. A prime example is the interplay between immune and endothelial cells, which led to the approval of anti-vascular endothelial growth factor-therapy combined with immune checkpoint inhibitors and classical chemotherapy in non-small cell lung cancer. Hence, a paradigm shift approach is to characterize the crosstalk between different non-malignant components of the TME and understand their role in tumorigenesis. In this perspective, we discuss the interplay between nerves and immune cells within the TME. In particular, we focus on exosomes and microRNAs as a systemic, rapid and dynamic communication channel between tumor cells, nerves and immune cells contributing to cancer progression. Finally, we discuss how combinatorial therapies blocking this tumorigenic cross-talk could lead to improved outcomes for cancer patients.

scholarly journals MCEMP1 as a Tumor Microenvironment and Immune Infiltration Related Gene for Prognostic Prediction in Advanced Gastric Cancer

2021 ◽  
Author(s):  
Daijun Wang ◽  
Yanmei Gu ◽  
Yang Zhao ◽  
Yumin Li
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Advanced Gastric Cancer ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Tissue Samples ◽  
Protein Protein Interaction ◽  
Immunotherapy Target

Abstract Background Tumor microenvironment (TME) has displayed profound clinical significance in cancer progression, prognosis and the efficacy of immunotherapy. However, the overall characteristics of TME in patients with advanced gastric cancer (AGC) have not been intensively studied. In order to get a more comprehensive understanding, this study aimed to investigate TME-related prognostic genes in patients with AGC based on bioinformatics, combined with histological verification.Methods Transcriptome and clinical data on stage III/IV GC were obtained from The Cancer Genome Atlas (TCGA) database. The data of stromal, immune scores and 22 infiltrating immune cells from AGC samples were evaluated by ESTIMATE and CIBERSORT algorithms. Then, mast cell-expressed membrane protein 1 (MCEMP1) was focused by integrated protein-protein interaction (PPI) network and Cox regression. The survival and expression analysis of MCEMP1 was evaluated and verified in tissues by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR).Results There was a positive correlation between TME scores and pathological grades. A total of 666 TME-related differential genes were screened. MCEMP1 was identified as a predictive factor related to the prognosis of AGC both in TCGA database and tissue samples. Further analysis indicated that MCEMP1 was involved in regulating pathways of immune activities. The results of CIBERSORT demonstrated that MCEMP1 expression was significantly correlated with the proportion of 8 kinds of infiltrating immune cells. Conclusion As a TME-related prognostic gene, MCEMP1 might play a crucial role in remodeling immune infiltrates in AGC patients, which might be a potential immunotherapy target for patients with AGC.

scholarly journals Single-cell Map of Diverse Immune Phenotypes Driven by the Tumor Microenvironment

2017 ◽  
Author(s):  
Elham Azizi ◽  
Ambrose J. Carr ◽  
George Plitas ◽  
Andrew E. Cornish ◽  
Catherine Konopacki ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Cell ◽  
Phenotypic Diversity ◽  
Macrophage Polarization ◽  
Sequencing Data ◽  
Significant Similarity

SUMMARYKnowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We created an immune map of breast cancer using single-cell RNA-seq data from 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph node. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous tumor-specific phenotypic expansions driven by environmental cues. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer, with important implications for characterizing tumor-infiltrating immune cells.

scholarly journals A bioengineered organotypic prostate model for the study of tumor microenvironment-induced immune cell activation

2020 ◽  
Vol 12 (10) ◽  
pp. 250-262
Author(s):  
Sheena C Kerr ◽  
Molly M Morgan ◽  
Amani A Gillette ◽  
Megan K Livingston ◽  
Karina M Lugo-Cintron ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cell Activation ◽  
Tumor Response ◽  
Immune Cell ◽  
Interleukin 1 ◽  
Cell Phenotypes

Abstract The prostate tumor microenvironment (TME) is strongly immunosuppressive; it is largely driven by alteration in cell phenotypes (i.e. tumor-associated macrophages and exhausted cytotoxic T cells) that result in pro-tumorigenic conditions and tumor growth. A greater understanding into how these altered immune cell phenotypes are developed and could potentially be reversed would provide important insights into improved treatment efficacy for prostate cancer. Here, we report a microfluidic model of the prostate TME that mimics prostate ducts across various stages of prostate cancer progression, with associated stroma and immune cells. Using this platform, we exposed immune cells to a benign prostate TME or a metastatic prostate TME and investigated their metabolism, gene and cytokine expression. Immune cells exposed to the metastatic TME showed metabolic differences with a higher redox ratio indicating a switch to a more glycolytic metabolic profile. These cells also increased expression of pro-tumor response cytokines that have been shown to increase cell migration and angiogenesis such as Interleukin-1 (IL-1) a and Granulocyte-macrophage colony-stimulating factor (GM-CSF). Lastly, we observed decreased TLR, STAT signaling and TRAIL expression, suggesting that phenotypes derived from exposure to the metastatic TME could have an impaired anti-tumor response. This platform could provide a valuable tool for studying immune cell phenotypes in in vitro tumor microenvironments.

Sign in / Sign up

Export Citation Format

Share Document