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 ◽  
...  

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.

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 445 ◽  
Author(s):  
Javier Mora ◽  
Christina Mertens ◽  
Julia K. Meier ◽  
Dominik C. Fuhrmann ◽  
Bernhard Brüne ◽  
...  

The inflammatory tumor microenvironment is an important regulator of carcinogenesis. Tumor-infiltrating immune cells promote each step of tumor development, exerting crucial functions from initiation, early neovascularization, to metastasis. During tumor outgrowth, tumor-associated immune cells, including myeloid cells and lymphocytes, acquire a tumor-supportive, anti-inflammatory phenotype due to their interaction with tumor cells. Microenvironmental cues such as inflammation and hypoxia are mainly responsible for creating a tumor-supportive niche. Moreover, it is becoming apparent that the availability of iron within the tumor not only affects tumor growth and survival, but also the polarization of infiltrating immune cells. The interaction of tumor cells and infiltrating immune cells is multifaceted and complex, finally leading to different activation phenotypes of infiltrating immune cells regarding their functional heterogeneity and plasticity. In recent years, it was discovered that these phenotypes are mainly implicated in defining tumor outcome. Here, we discuss the role of the metabolic activation of both tumor cells and infiltrating immune cells in order to adapt their metabolism during tumor growth. Additionally, we address the role of iron availability and the hypoxic conditioning of the tumor with regard to tumor growth and we describe the relevance of therapeutic strategies to target such metabolic characteristics.


2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 8-11 ◽  
Author(s):  
Paola Nisticò ◽  
Gennaro Ciliberto

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Hong Zhong ◽  
Minjuan Ma ◽  
Tingming Liang ◽  
Li Guo

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2141
Author(s):  
Katie Alexander ◽  
Charles O. Elson

Bacteria and mammals have co-evolved with one another over millennia, and it has become impossible to interpret mucosal immunity without taking the microbiota into consideration. In fact, the primary role of the mucosal immune system is regulating homeostasis and the host relationship with the microbiota. Bacteria are no longer seen as simply invading pathogens, but rather a necessary component to one’s own immune response. On the one hand, the microbiota is a vital educator of immune cells and initiator of beneficial responses; but, on the other, dysbiosis of microbiota constituents are associated with inflammation and autoimmune disorders. In this review, we will consider recent advances in the understanding of how the microbiota influences host mucosal immunity, particularly the initial development of the immune response and its implications.


2020 ◽  
Vol 133 (1) ◽  
pp. 49-64 ◽  
Author(s):  
Emanuele Chisari ◽  
Laura Rehak ◽  
Wasim S Khan ◽  
Nicola Maffulli

Abstract Introduction The role of the immune system in tendon healing relies on polymorphonucleocytes, mast cells, macrophages and lymphocytes, the ‘immune cells’ and their cytokine production. This systematic review reports how the immune system affects tendon healing. Sources of data We registered our protocol (registration number: CRD42019141838). After searching PubMed, Embase and Cochrane Library databases, we included studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results. The PRISMA guidelines were applied, and risk of bias and the methodological quality of the included studies were assessed. We excluded all the articles with high risk of bias and/or low quality after the assessment. We included 62 articles assessed as medium or high quality. Areas of agreement Macrophages are major actors in the promotion of proper wound healing as well as the resolution of inflammation in response to pathogenic challenge or tissue damage. The immune cells secrete cytokines involving both pro-inflammatory and anti-inflammatory factors which could affect both healing and macrophage polarization. Areas of controversy The role of lymphocytes, mast cells and polymorphonucleocytes is still inconclusive. Growing points The immune system is a major actor in the complex mechanism behind the healing response occurring in tendons after an injury. A dysregulation of the immune response can ultimately lead to a failed healing response. Areas timely for developing research Further studies are needed to shed light on therapeutic targets to improve tendon healing and in managing new way to balance immune response.


2020 ◽  
Vol 21 (1) ◽  
pp. 75-82
Author(s):  
Mladen Pavlovic ◽  
Ivan Jovanovic ◽  
Nebojsa Arsenijevic

AbstractCytokines are small pleiotropic polypeptids secreted dominantly by the cells of the immune system. These polypeptids are main mediators of innate and acquired immunity, responsible for clonal expansion and differentiation of immune cells, initiation of immune response and enhancing of effector functions of leukocytes. Cytokine-related effects are most studied in the fields of inflammation, immunology, and cancer biology. In this review we discuss one of the most intriguing, recently discovered proinflammatory cytokine, interleukin 32.


2020 ◽  
Vol 21 (12) ◽  
pp. 4346 ◽  
Author(s):  
Anthony M. Battram ◽  
Mireia Bachiller ◽  
Beatriz Martín-Antonio

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.


2021 ◽  
Vol 7 (1) ◽  
pp. 4
Author(s):  
Heidi Schwarzenbach ◽  
Peter B. Gahan

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.


2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Hongwei Chen

Cancer is a devastating disease that suffered so many lives and families throughout of the world, and is becoming an increasing burden to our society. Thanks to the advances in both basic cancer biology and clinical diagnostic/therapeutic treatments, cancer patients’ mortality has been significantly decreased in the past decades. Specifically, recent breakthrough in cancer immunology and immunotherapy has shed a bright light for cancer patients to guide them to fight the cancer via harnessing their own immune system, as some patients even with advanced diseases showed long-term remission and durable responses after immunotherapy. Although this new cancer treatment can only benefit a subset of cancer patients, it clearly suggests to us that patient’s immune cells have the capability to fight against cancer. It is just a matter of how to use them. As a peer-reviewed open journal, the Journal of Oncology Research is dedicated to publish most cutting edge research with a focus on how cancer invades our immune system and how to develop effective strategies to reverse this invasion. Journal of Oncology Research aims to discover innovative methods, theories and studies in Oncology by publishing original articles, case studies and comprehensive reviews. We hope that Journal of Oncology Research will become an important platform for our scientists to share their exciting results and for our readers to seek fertile and reliable source of information. We will look for research in the following topics, but not limited:Cancer immunology and immunotherapy: This topic will cover new basic molecular and cellular mechanisms of interactions between tumor cells and immune system; new therapeutic combinations to boost cancer immunotherapy; and new prognostic indicators.Tumor-derived exosomes: This topic will cover new findings in understanding how tumor-derived exosomes interact with immune system, tumor immunity, and tumor-associated fibroblasts.Metastasis: This topic will include new findings in investigating novel mechanisms of cancer metastasis including how tumor cells invade primary tissues, exit from circulation into distant organs, and promote niche formation in metastatic organs.Microbiome and cancer: This topic will cover the new investigations in understanding the role of microbiota in cancer progression and therapeutic outcomes.Cancer nanotechnology: This topic will include new findings in using nanotechnology for early diagnosis, developing novel nanomedicines for targeting and reprogramming suppressive immune cells, and generating immunogenic cell death in combination with cancer immunotherapy.Tumor markers and cancer early diagnosis: This topic will cover the identification of novel markers from liquid biopsy including blood-based assessment of tumor-derived and non-tumor derived exosomes to identify a molecular signature that can inform the disease status of cancer.


2020 ◽  
Vol 16 ◽  
Author(s):  
Behnam Emamgolizadeh Gurt Tapeh ◽  
Mohammad Sadegh Hashemzadeh ◽  
Ali Mir Hoseini

Aims: Encouraging results have been indicated preclinically and in patients using the bacterial super antigen. This review article intends to summarize the role of the super antigens that have been recently used in the treatment of cancer. In addition, the vector systems including lentiviral vectors, adeno-associated vector systems and retroviral vectors that are increasingly being used in basic and applied research were discussed. Most importantly, the new CRISPR technique has also been discussed in this literature review. Discussion: More successful therapies can be achieved by manipulating bacterial vector systems through incorporating genes related to the super antigens and cytokines. The products of SAg and cytokine genes contributes to the strong stimulation of immune system against tumor cells. They bind to MHC II molecules as well as the V beta regions of TCR and lead to the production of IL2 and other cytokines, the activation of antigen-presenting cells and T lymphocytes. Additionally, super antigens can be used to eradicate tumor cells. Better results in cancer treatment can be achieved by transferring super antigen genes and subsequent strong immune stimulation along with other cancer immunotherapy agents. Conclusion: Super antigens induce the proliferation of T lymphocytes and antigen-presenting cells by binding to MHCII molecules and V beta regions in T cell receptors. Therefore, the presentation of tumor cell antigens is increased. Additionally, the production of important cytokines by T cells and APCs contributes to the stimulation of immune response against tumor cells. The manipulation of bacterial vector systems through incorporating genes related to SAgs and other immune response factors is a good strategy for immune system stimulating and eradicating of tumor cells along with other immunotherapy agents.


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