scholarly journals Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 46 ◽  
Author(s):  
Anfray ◽  
Ummarino ◽  
Andón ◽  
Allavena
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Tumor Tissue ◽  
Tumor Response ◽  
Current Knowledge ◽  
Tumor Associated Macrophages ◽  
Cancer Proliferation ◽  
The Past ◽  
Active Research ◽  
Novel Therapeutic Strategies

: Established evidence demonstrates that tumor-infiltrating myeloid cells promote rather than stop-cancer progression. Tumor-associated macrophages (TAMs) are abundantly present at tumor sites, and here they support cancer proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Their pro-tumor activities hamper the response of cancer patients to conventional therapies, such as chemotherapy or radiotherapy, and also to immunotherapies based on checkpoint inhibition. Active research frontlines of the last years have investigated novel therapeutic strategies aimed at depleting TAMs and/or at reprogramming their tumor-promoting effects, with the goal of re-establishing a favorable immunological anti-tumor response within the tumor tissue. In recent years, numerous clinical trials have included pharmacological strategies to target TAMs alone or in combination with other therapies. This review summarizes the past and current knowledge available on experimental tumor models and human clinical studies targeting TAMs for cancer treatment.

scholarly journals Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

2020 ◽  
Vol 9 (10) ◽  
pp. 3226
Author(s):  
Cristina Belgiovine ◽  
Elisabeth Digifico ◽  
Clément Anfray ◽  
Aldo Ummarino ◽  
Fernando Torres Andón
Keyword(s):  
Current Knowledge ◽  
Cancer Therapies ◽  
Combination Therapies ◽  
Tumor Associated Macrophages ◽  
Effector Cells ◽  
Anti Cancer ◽  
Novel Therapeutic Strategies ◽  
The Right ◽  
Do The Right Thing ◽  
Cytotoxic Effector

In the last decade, it has been well-established that tumor-infiltrating myeloid cells fuel not only the process of carcinogenesis through cancer-related inflammation mechanisms, but also tumor progression, invasion, and metastasis. In particular, tumor-associated macrophages (TAMs) are the most abundant leucocyte subset in many cancers and play a major role in the creation of a protective niche for tumor cells. Their ability to generate an immune-suppressive environment is crucial to escape the immune system and to allow the tumor to proliferate and metastasize to distant sites. Conventional therapies, including chemotherapy and radiotherapy, are often not able to limit cancer growth due to the presence of pro-tumoral TAMs; these are also responsible for the failure of novel immunotherapies based on immune-checkpoint inhibition. Several novel therapeutic strategies have been implemented to deplete TAMs; however, more recent approaches aim to use TAMs themselves as weapons to fight cancer. Exploiting their functional plasticity, the reprogramming of TAMs aims to convert immunosuppressive and pro-tumoral macrophages into immunostimulatory and anti-tumor cytotoxic effector cells. This shift eventually leads to the reconstitution of a reactive immune landscape able to destroy the tumor. In this review, we summarize the current knowledge on strategies able to reprogram TAMs with single as well as combination therapies.

scholarly journals Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 114
Author(s):  
Lisa Linck-Paulus ◽  
Claus Hellerbrand ◽  
Anja K. Bosserhoff ◽  
Peter Dietrich
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
The Future ◽  
Associated Proteins ◽  
Cancer Types ◽  
Novel Therapeutic Strategies

In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

scholarly journals Mechanisms of Metastatic Tumor Dormancy and Implications for Cancer Therapy

2019 ◽  
Vol 20 (24) ◽  
pp. 6158 ◽  
Author(s):  
Christiana M. Neophytou ◽  
Theodora-Christina Kyriakou ◽  
Panagiotis Papageorgis
Keyword(s):  
Cancer Progression ◽  
Current Knowledge ◽  
Metastatic Cancer ◽  
Metastatic Tumor ◽  
Tumor Dormancy ◽  
Secondary Site ◽  
Quiescent State ◽  
Metastatic Cells ◽  
Multistep Process ◽  
Novel Therapeutic Strategies

Metastasis, a multistep process during which tumor cells disseminate to secondary organs, represents the main cause of death for cancer patients. Metastatic dormancy is a late stage during cancer progression, following extravasation of cells at a secondary site, where the metastatic cells stop proliferating but survive in a quiescent state. When the microenvironmental conditions are favorable, they re-initiate proliferation and colonize, sometimes years after treatment of the primary tumor. This phenomenon represents a major clinical obstacle in cancer patient care. In this review, we describe the current knowledge regarding the genetic or epigenetic mechanisms that are activated by cancer cells that either sustain tumor dormancy or promote escape from this inactive state. In addition, we focus on the role of the microenvironment with emphasis on the effects of extracellular matrix proteins and in factors implicated in regulating dormancy during colonization to the lungs, brain, and bone. Finally, we describe the opportunities and efforts being made for the development of novel therapeutic strategies to combat metastatic cancer, by targeting the dormancy stage.

scholarly journals Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses

2020 ◽  
Vol 12 (530) ◽  
pp. eaax6337 ◽  
Author(s):  
Jesse M. Jaynes ◽  
Rushikesh Sable ◽  
Michael Ronzetti ◽  
Wendy Bautista ◽  
Zachary Knotts ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Selective Reduction ◽  
Mannose Receptor ◽  
Tumor Associated Macrophages ◽  
Host Defense Peptides ◽  
Surface Receptors ◽  
Effective Combination

Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this immune response is co-opted into contributing toward tumor growth instead of preventing its progression. We seek to reestablish an antitumor immune response by selectively targeting surface receptors and endogenous signaling processes of the macrophage subtypes driving cancer progression. RP-182 is a synthetic 10-mer amphipathic analog of host defense peptides that selectively induces a conformational switch of the mannose receptor CD206 expressed on TAMs displaying an M2-like phenotype. RP-182–mediated activation of this receptor in human and murine M2-like macrophages elicits a program of endocytosis, phagosome-lysosome formation, and autophagy and reprograms M2-like TAMs to an antitumor M1-like phenotype. In syngeneic and autochthonous murine cancer models, RP-182 suppressed tumor growth, extended survival, and was an effective combination partner with chemo- or immune checkpoint therapy. Antitumor activity of RP-182 was also observed in CD206high patient-derived xenotransplantation models. Mechanistically, via selective reduction of immunosuppressive M2-like TAMs, RP-182 improved adaptive and innate antitumor immune responses, including increased cancer cell phagocytosis by reprogrammed TAMs.

scholarly journals Group therapy on in utero colonization: seeking common truths and a way forward

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Rachel B. Silverstein ◽  
Indira U. Mysorekar
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Human Microbiome ◽  
In Utero ◽  
Antibiotic Usage ◽  
Human Fetuses ◽  
Genetic Composition ◽  
The Past ◽  
Interdependent Relationships ◽  
Broad Understanding

AbstractThe human microbiome refers to the genetic composition of microorganisms in a particular location in the human body. Emerging evidence over the past many years suggests that the microbiome constitute drivers of human fate almost at par with our genome and epigenome. It is now well accepted after decades of disbelief that a broad understanding of human development, health, physiology, and disease requires understanding of the microbiome along with the genome and epigenome. We are learning daily of the interdependent relationships between microbiome/microbiota and immune responses, mood, cancer progression, response to therapies, aging, obesity, antibiotic usage, and overusage and much more. The next frontier in microbiome field is understanding when does this influence begin? Does the human microbiome initiate at the time of birth or are developing human fetuses already primed with microbes and their products in utero. In this commentary, we reflect on evidence gathered thus far on this question and identify the unknown common truths. We present a way forward to continue understanding our microbial colleagues and our interwoven fates.

scholarly journals The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy?

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sonja S. Mojsilovic ◽  
Slavko Mojsilovic ◽  
Victor H. Villar ◽  
Juan F. Santibanez
Keyword(s):  
Cancer Progression ◽  
Tumor Tissue ◽  
Acid Metabolism ◽  
Cell Types ◽  
Innate Immune ◽  
High Plasticity ◽  
Tumor Associated Macrophages ◽  
Cell Therapies ◽  
Physical Barriers ◽  
Cancer Immunotherapies

Besides transformed cells, the tumors are composed of various cell types that contribute to undesirable tumor progression. Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in the tumor microenvironment (TME). Within the TME, TAMs exhibit high plasticity and undergo specific functional metabolic alterations according to the availability of tumor tissue oxygen and nutrients, thus further contributing to tumorigenesis and cancer progression. Here, we review the main functional TAM metabolic patterns influenced by TME, including glycolysis, amino acid, and fatty acid metabolism. Moreover, this review discusses antitumor immunotherapies that affect TAM functionality by inducing cell repolarizing and metabolic profiles towards an antitumoral phenotype. Also, new macrophage-based cell therapeutic technologies recently developed using chimeric antigen receptor bioengineering are exposed, which may overcome all solid tumor physical barriers impeding the current adoptive cell therapies and contribute to developing novel cancer immunotherapies.

Monocytes in the Tumor Microenvironment

2021 ◽  
Vol 16 (1) ◽  
pp. 93-122
Author(s):  
Stefano Ugel ◽  
Stefania Canè ◽  
Francesco De Sanctis ◽  
Vincenzo Bronte
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Tumor Cells ◽  
Current Knowledge ◽  
Tumor Development ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
The Past ◽  
Immunosuppressive Tumor Microenvironment ◽  
Antigen Presenting

Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a multifaceted immune-suppressive network whose nature is progressively shaped by systemic and local cues during tumor development. Monocytes bridge innate and adaptive immune responses and can affect the tumor microenvironment through various mechanisms that induce immune tolerance, angiogenesis, and increased dissemination of tumor cells. Yet monocytes can also give rise to antitumor effectors and activate antigen-presenting cells. This yin-yang activity relies on the plasticity of monocytes in response to environmental stimuli. In this review, we summarize current knowledge of the ontogeny, heterogeneity, and functions of monocytes and monocyte-derived cells in cancer, pinpointing the main pathways that are important for modeling the immunosuppressive tumor microenvironment.

scholarly journals Tumor-Associated Microbiome: Where Do We Stand?

2021 ◽  
Vol 22 (3) ◽  
pp. 1446
Author(s):  
Marc Oliva ◽  
Nuria Mulet-Margalef ◽  
Maria Ochoa-De-Olza ◽  
Stefania Napoli ◽  
Joan Mas ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Clinical Utility ◽  
Checkpoint Inhibitors ◽  
Human Microbiome ◽  
Proof Of Concept ◽  
The Past ◽  
Immune Contexture ◽  
Potential Clinical Utility

The study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome—microbe communities located either in the tumor or within its body compartment—seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies.

scholarly journals Evaluation of MicroRNAs Regulating Anoikis Pathways and Its Therapeutic Potential

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sharan Malagobadan ◽  
Noor Hasima Nagoor
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Therapeutic Potential ◽  
Research Question ◽  
Therapeutic Strategies ◽  
Anoikis Resistance ◽  
The Past ◽  
Cancer Types ◽  
Novel Therapeutic Strategies ◽  
Survival Mechanisms

Dysregulation of microRNAs (miRNAs) has been implicated in almost every known survival mechanisms utilized by cancer cells. One of such mechanisms, anoikis resistance, plays a pivotal role in enabling metastasis by allowing cancer cells to circumvent cell death induced by lack of attachment. Understanding how miRNAs regulate the various anoikis pathways has become the research question of increasing number of studies published in the past years. Through these studies, a growing list of miRNAs has been identified to be important players in promoting either anoikis or resistance to anoikis. In this review, we will be focusing on these miRNAs and how the findings from those studies can contribute to novel therapeutic strategies against cancer progression. We will be examining miRNAs that have been found to promote anoikis sensitivity in numerous cancer types followed by miRNAs that inhibit anoikis. In addition, we will also be taking a look at major signaling pathways involved in the action of the each of these miRNAs to gain a better understanding on how miRNAs regulate anoikis.

scholarly journals The Dual Role of HLA-G in Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Nathalie Rouas-Freiss ◽  
Philippe Moreau ◽  
Joel LeMaoult ◽  
Edgardo D. Carosella
Keyword(s):  
Cancer Progression ◽  
Current Knowledge ◽  
Malignant Cell ◽  
Current Data ◽  
Dual Role ◽  
Tumor Escape ◽  
The Past ◽  
Active Structures ◽  
Tumor Escape Mechanism

We here review the current data on the role of HLA-G in cancer based on recent findings of an unexpected antitumor activity of HLA-G in hematological malignancies. For the past decade, HLA-G has been described as a tumor-escape mechanism favoring cancer progression, and blocking strategies have been proposed to counteract it. Aside from these numerous studies on solid tumors, recent data showed that HLA-G inhibits the proliferation of malignant B cells due to the interaction between HLA-G and its receptor ILT2, which mediates negative signaling on B cell proliferation. These results led to the conjecture that, according to the malignant cell type, HLA-G should be blocked or conversely induced to counteract tumor progression. In this context, we will here present (i) the dual role of HLA-G in solid and liquid tumors with special emphasis on (ii) the HLA-G active structures and their related ILT2 and ILT4 receptors and (iii) the current knowledge on regulatory mechanisms of HLA-G expression in tumors.

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