scholarly journals Exosomes in Immune Regulation

2021 ◽  
Vol 7 (1) ◽  
pp. 4
Author(s):  
Heidi Schwarzenbach ◽  
Peter B. Gahan
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Cells ◽  
Intercellular Communication ◽  
Immune Regulation ◽  
Immune Escape ◽  
Cytotoxic Responses

Exosomes, small extracellular vesicles mediate intercellular communication by transferring their cargo including DNA, RNA, proteins and lipids from cell to cell. Notably, in the immune system, they have protective functions. However in cancer, exosomes acquire new, immunosuppressive properties that cause the dysregulation of immune cells and immune escape of tumor cells supporting cancer progression and metastasis. Therefore, current investigations focus on the regulation of exosome levels for immunotherapeutic interventions. In this review, we discuss the role of exosomes in immunomodulation of lymphoid and myeloid cells, and their use as immune stimulatory agents to elicit specific cytotoxic responses against the tumor.

scholarly journals The Role of the Innate Immune System in Cancer Dormancy and Relapse

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5621
Author(s):  
Noah M. Chernosky ◽  
Ilaria Tamagno
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Innate Immune System ◽  
Immune Escape ◽  
Disease Process ◽  
Innate Immune ◽  
Cancer Dormancy

Metastatic spread and recurrence are intimately linked to therapy failure, which remains an overarching clinical challenge for patients with cancer. Cancer cells often disseminate early in the disease process and can remain dormant for years or decades before re-emerging as metastatic disease, often after successful treatment. The interactions of dormant cancer cells and their metastatic niche, comprised of various stromal and immune cells, can determine the length of time that cancer cells remain dormant, as well as when they reactivate. New studies are defining how innate immune cells in the primary tumor may be corrupted to help facilitate many aspects of dissemination and re-emergence from a dormant state. Although the scientific literature has partially shed light on the drivers of immune escape in cancer, the specific mechanisms regulating metastasis and dormancy in the context of anti-tumor immunity are still mostly unknown. This review follows the journey of metastatic cells from dissemination to dormancy and the onset of metastatic outgrowth and recurrent tumor development, with emphasis on the role of the innate immune system. To this end, further research identifying how immune cells interact with cancer cells at each step of cancer progression will pave the way for new therapies that target the reactivation of dormant cancer cells into recurrent, metastatic cancers.

scholarly journals Emerging Role of Extracellular Vesicles in Immune Regulation and Cancer Progression

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3563
Author(s):  
Sonam Mittal ◽  
Prachi Gupta ◽  
Pradeep Chaluvally-Raghavan ◽  
Sunila Pradeep
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Regulation ◽  
Therapeutic Intervention ◽  
Tumor Stroma ◽  
Membrane Bound ◽  
Regulatory Functions ◽  
Extracellular Environment ◽  
Insight Into

The development of effective therapies for cancer treatment requires a better understanding of the tumor extracellular environment and a dynamic interaction between tumor cells, the cells of the immune system, and the tumor stroma. Increasing evidence suggests that extracellular vesicles play an important role in this interaction. Extracellular vesicles are nanometer-sized membrane-bound vesicles secreted by various types of cells that facilitate intracellular communication by transferring proteins, various lipids, and nucleic acids, especially miRNAs, between cells. Extracellular vesicles play discrete roles in the immune regulatory functions, such as antigen presentation, and activation or suppression of immune cells. Achieving therapeutic intervention through targeting of extracellular vesicles is a crucial area of research now. Thus, a deeper knowledge of exosome biology and the molecular mechanism of immune regulation is likely to provide significant insight into therapeutic intervention utilizing extracellular vesicles to combat this dreadful disease. This review describes the recent updates on immune regulation by extracellular vesicles in cancer progression and possible use in cancer therapy.

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 The role of extracellular vesicles in phenotypic cancer transformation

2013 ◽  
Vol 47 (3) ◽  
pp. 197-205 ◽  
Author(s):  
Eva Ogorevc ◽  
Veronika Kralj-Iglic ◽  
Peter Veranic
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Tumour Growth ◽  
Gene Mutations ◽  
Membrane Structures ◽  
New Findings ◽  
Genetic Origins ◽  
Phenotypic Transformation

AbstractBackground.Cancer has traditionally been considered as a disease resulting from gene mutations. New findings in biology are challenging gene-centered explanations of cancer progression and redirecting them to the non-genetic origins of tumorigenicity. It has become clear that intercellular communication plays a crucial role in cancer progression. Among the most intriguing ways of intercellular communication is that via extracellular vesicles (EVs). EVs are membrane structures released from various types of cells. After separation from the mother membrane, EVs become mobile and may travel from the extracellular space to blood and other body fluids.Conclusions.Recently it has been shown that tumour cells are particularly prone to vesiculation and that tumour-derived EVs can carry proteins, lipids and nucleic acids causative of cancer progression. The uptake of tumour-derived EVs by noncancerous cells can change their normal phenotype to cancerous. The suppression of vesiculation could slow down tumour growth and the spread of metastases. The purpose of this review is to highlight examples of EVmediated cancer phenotypic transformation in the light of possible therapeutic applications.

scholarly journals Exosomes and Their Role in Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Liu ◽  
Ke Shi ◽  
Yong Chen ◽  
Xianrui Wu ◽  
Zheng Chen ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Research Progress ◽  
Chemotherapeutic Drugs ◽  
Other Substances

Exosomes from extracellular vesicles can activate or inhibit various signaling pathways by transporting proteins, lipids, nucleic acids and other substances to recipient cells. In addition, exosomes are considered to be involved in the development and progression of tumors from different tissue sources in numerous ways, including remodeling of the tumor microenvironment, promoting angiogenesis, metastasis, and invasion, and regulating the immune escape of tumor cells. However, the precise molecular mechanisms by which exosomes participate in these different processes remains unclear. In this review, we describe the research progress of tumor cell-derived exosomes in cancer progression. We also discuss the prospects of the application of exosomes combined with nanoengineered chemotherapeutic drugs in the treatment of cancer.

scholarly journals Role of Exosomes in Prostate Cancer Metastasis

2021 ◽  
Vol 22 (7) ◽  
pp. 3528
Author(s):  
Theresa Akoto ◽  
Sharanjot Saini
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Cancer Metastasis ◽  
Disseminated Tumor Cells ◽  
Bilayer Membrane ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Metastasis

Prostate cancer remains a life-threatening disease among men worldwide. The majority of PCa-related mortality results from metastatic disease that is characterized by metastasis of prostate tumor cells to various distant organs, such as lung, liver, and bone. Bone metastasis is most common in prostate cancer with osteoblastic and osteolytic lesions. The precise mechanisms underlying PCa metastasis are still being delineated. Intercellular communication is a key feature underlying prostate cancer progression and metastasis. There exists local signaling between prostate cancer cells and cells within the primary tumor microenvironment (TME), in addition to long range signaling wherein tumor cells communicate with sites of future metastases to promote the formation of pre-metastatic niches (PMN) to augment the growth of disseminated tumor cells upon metastasis. Over the last decade, exosomes/ extracellular vesicles have been demonstrated to be involved in such signaling. Exosomes are nanosized extracellular vesicles (EVs), between 30 and 150 nm in thickness, that originate and are released from cells after multivesicular bodies (MVB) fuse with the plasma membrane. These vesicles consist of lipid bilayer membrane enclosing a cargo of biomolecules, including proteins, lipids, RNA, and DNA. Exosomes mediate intercellular communication by transferring their cargo to recipient cells to modulate target cellular functions. In this review, we discuss the contribution of exosomes/extracellular vesicles in prostate cancer progression, in pre-metastatic niche establishment, and in organ-specific metastases. In addition, we briefly discuss the clinical significance of exosomes as biomarkers and therapeutic agents.

scholarly journals Immunometabolism Modulation in Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 798
Author(s):  
Ezequiel Monferrer ◽  
Sabina Sanegre ◽  
Isaac Vieco-Martí ◽  
Amparo López-Carrasco ◽  
Fernando Fariñas ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Tumor Cells ◽  
Immune Cells ◽  
Therapeutic Intervention ◽  
Cancer Biology ◽  
Metabolic Regulation ◽  
Tumor Development ◽  
Molecular Bases

The study of cancer biology should be based around a comprehensive vision of the entire tumor ecosystem, considering the functional, bioenergetic and metabolic state of tumor cells and those of their microenvironment, and placing particular importance on immune system cells. Enhanced understanding of the molecular bases that give rise to alterations of pathways related to tumor development can open up new therapeutic intervention opportunities, such as metabolic regulation applied to immunotherapy. This review outlines the role of various oncometabolites and immunometabolites, such as TCA intermediates, in shaping pro/anti-inflammatory activity of immune cells such as MDSCs, T lymphocytes, TAMs and DCs in cancer. We also discuss the extraordinary plasticity of the immune response and its implication in immunotherapy efficacy, and highlight different therapeutic intervention possibilities based on controlling the balanced systems of specific metabolites with antagonistic functions.

scholarly journals The Role of Innate Immune Cells in Tumor Invasion and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5885
Author(s):  
Yu-Kuan Huang ◽  
Rita A. Busuttil ◽  
Alex Boussioutas
Keyword(s):  
Tumor Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Tumor Invasion ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Invasion And Metastasis ◽  
Immune Therapies

Metastasis is considered one of the hallmarks of cancer and enhanced tumor invasion and metastasis is significantly associated with cancer mortality. Metastasis occurs via a series of integrated processes involving tumor cells and the tumor microenvironment. The innate immune components of the microenvironment have been shown to engage with tumor cells and not only regulate their proliferation and survival, but also modulate the surrounding environment to enable cancer progression. In the era of immune therapies, it is critical to understand how different innate immune cell populations are involved in this process. This review summarizes recent literature describing the roles of innate immune cells during the tumor metastatic cascade.

scholarly journals Differential Role of PD-1 Expressed by Various Immune and Tumor Cells in the Tumor Immune Microenvironment: Expression, Function, Therapeutic Efficacy, and Resistance to Cancer Immunotherapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Myeong Joon Kim ◽  
Sang-Jun Ha
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Escape ◽  
Immune Microenvironment ◽  
Patients With Cancer ◽  
Tumor Immune Microenvironment

In the tumor immune microenvironment (TIME), tumor cells interact with various cells and operate various strategies to avoid antitumor immune responses. These immune escape strategies often make the TIME resistant to cancer immunotherapy. Neutralizing immune escape strategies is necessary to overcome resistance to cancer immunotherapy. Immune checkpoint receptors (ICRs) expressed in effector immune cells inhibit their effector function via direct interaction with immune checkpoint ligands (ICLs) expressed in tumor cells. Therefore, blocking ICRs or ICLs has been developed as a promising cancer immunotherapy by reinvigorating the function of effector immune cells. Among the ICRs, programmed cell death 1 (PD-1) has mainly been antagonized to enhance the survival of human patients with cancer by restoring the function of tumor-infiltrating (TI) CD8+ T cells. It has been demonstrated that PD-1 is expressed not only in TI CD8+ T cells, but also in other TI immune cells and even tumor cells. While PD-1 suppresses the function of TI CD8+ T cells, it is controversial whether PD-1 suppresses or amplifies the suppressive function of TI-suppressive immune cells (e.g., regulatory T cells, tumor-associated macrophages, and myeloid cells). There is also controversy regarding the role of tumor-expressing PD-1. Therefore, a precise understanding of the expression pattern and function of PD-1 in each cell subset is important for improving the efficacy of cancer immunotherapy. Here, we review the differential role of PD-1 expressed by various TI immune cells and tumor cells. We focused on how cell-type-specific ablation or blockade of PD-1 affects tumor growth in a murine tumor model. Furthermore, we will also describe how the blockade of PD-1 acts on TI immune cells in human patients with cancer.

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