Volume 3 (2019)

Gold Nanoparticles sensitize pancreatic cancer cells to gemcitabine

Yanyan Huai1, Yushan Zhang1, Xunhao Xiong1, Shamik Das2, Resham Bhattacharya2 and Priyabrata Mukherjee1,2

INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. The mortality rate closely parallels that of incidence [1][2]. The current standard of care for advanced stage PDAC patients includes

Unraveling the molecular principles by which ceramides commit cells to death

Shashank Dadsena1, Dina G. Hassan1 and Joost C.M. Holthuis1

EMERGENCE OF CERAMIDES AS TUMOR SUPPRESSOR LIPIDS Sphingolipids are unusually versatile membrane components that participate in mechanical stability, signaling, and molecular sorting. As the path to their production is paved

Immunosurveillance of cancer cell stress

Seila Lorenzo-Herrero1-3, Christian Sordo-Bahamonde1-3, Segundo González1-3 and Alejandro López-Soto1-3

Cancer development is tightly controlled by effector immune responses that recognize and eliminate malignantly transformed cells. Nonetheless, certain immune subsets, such as tumor-associated macrophages, have been described to promote tumor growth, unraveling a double-edge role of the immune system in cancer. Cell stress can modulate the crosstalk between immune cells and tumor cells, reshaping tumor immunogenicity and/or immune function and phenotype. Infiltrating immune cells are exposed to the challenging conditions typically present in the tumor microenvironment. In return, the myriad of signaling pathways activated in response to stress conditions may tip the balance toward stimulation of antitumor responses or immune-mediated tumor progression. Here, we explore how distinct situations of cellular stress influence innate and adaptive immunity and the consequent impact on cancer establishment and progression.

Myelopoiesis, metabolism and therapy: a crucial crossroads in cancer progression

Antonio Sica1,2, Valentina Guarneri3,4 and Alessandra Gennari5

INTRODUCTION The bone marrow (BM) is a primary lymphoid organ that hosts hematopoietic progenitors and presides over hematopoiesis, which is defined as the production of all types of blood cells.

Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicity

Maite Alvarez1,2, Itziar Otano1,2, Luna Minute1,2, Maria Carmen Ochoa1,2,3, Elisabeth Perez-Ruiz1,4, Ignacio Melero1,2,3,5,6 and Pedro Berraondo1,2,3

Inhibitory checkpoint blockade (ICB) immunotherapy has produced very significant advances in the fight against cancer (Figure 1). The synergistic combination of PD-1 and CTLA-4 blockade therapy has been successfully used

Immunometabolic cross-talk in the inflamed heart

Federica M. Marelli-Berg1,3 and Dunja Aksentijevic2,3

Inflammatory processes underlie many diseases associated with injury of the heart muscle, including conditions without an obvious inflammatory pathogenic component such as hypertensive and diabetic cardiomyopathy. Persistence of cardiac inflammation can cause irreversible structural and functional deficits. Some are induced by direct damage of the heart muscle by cellular and soluble mediators but also by metabolic adaptations sustained by the inflammatory microenvironment. It is well established that both cardiomyocytes and immune cells undergo metabolic reprogramming in the site of inflammation, which allow them to deal with decreased availability of nutrients and oxygen. However, like in cancer, competition for nutrients and increased production of signalling metabolites such as lactate initiate a metabolic cross-talk between immune cells and cardiomyocytes which, we propose, might tip the balance between resolution of the inflammation versus adverse cardiac remodeling. Here we review our current understanding of the metabolic reprogramming of both heart tissue and immune (...)

The role of epigenetics in hypothalamic energy balance control: implications for obesity

Arnaud Obri1 and Marc Claret1,2

INTRODUCTION The prevalence of obesity continues to increase worldwide. This trend is of concern because of its dramatic economic impact, concomitant decreased lifespan and increased comorbidities, such as hypertension, cardiovascular

Stress and catecholamines modulate the bone marrow microenvironment to promote tumorigenesis

Pauline Hanns1, Anna M. Paczulla1, Michael Medinger2, Martina Konantz1 and Claudia Lengerke1,2

High vascularization and locally secreted factors make the bone marrow (BM) microenvironment particularly hospitable for tumor cells and bones to a preferred metastatic site for disseminated cancer cells of different origins. Cancer cell homing and proliferation in the BM are amongst other regulated by complex interactions with BM niche cells (e.g. osteoblasts, endothelial cells and mesenchymal stromal cells (MSCs)), resident hematopoietic stem and progenitor cells (HSPCs) and pro-angiogenic cytokines leading to enhanced BM microvessel densities during malignant progression. Stress and catecholamine neurotransmitters released in response to activation of the sympathetic nervous system (SNS) reportedly modulate various BM cells and may thereby influence cancer progression. Here we review the role of catecholamines during tumorigenesis with particular focus on pro-tumorigenic effects mediated by the BM niche.

Remodeling of mitochondrial morphology and function: an emerging hallmark of cellular reprogramming

Anuj Rastogi1, Piyush Joshi2,3, Ela Contreras1 and Vivian Gama1,2,3,4

Research in the stem cell field has traditionally focused on understanding key transcriptional factors that provide pluripotent cell identity. However, much less is known about other critical non-transcriptional signaling networks that govern stem cell identity. Although we continue to gain critical insights into the mechanisms underlying mitochondrial morphology and function during cellular reprogramming – the process of reverting the fate of a differentiated cell into a stem cell, many uncertainties remain. Recent studies suggest an emerging landscape in which mitochondrial morphology and function have an active role in maintaining and regulating changes in cell identity. In this review, we will focus on these emerging concepts as crucial modulators of cellular reprogramming. Recognition of the widespread applicability of these concepts will increase our understanding of the mitochondrial mechanisms involved in cell identity, cell fate and disease.

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Myelopoiesis, metabolism and therapy: a crucial crossroads in cancer progression

Antonio Sica1,2, Valentina Guarneri3,4 and Alessandra Gennari5

INTRODUCTION The bone marrow (BM) is a primary lymphoid organ that hosts hematopoietic progenitors and presides over hematopoiesis, which is defined as the production of all types of blood cells.

Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicity

Maite Alvarez1,2, Itziar Otano1,2, Luna Minute1,2, Maria Carmen Ochoa1,2,3, Elisabeth Perez-Ruiz1,4, Ignacio Melero1,2,3,5,6 and Pedro Berraondo1,2,3

Inhibitory checkpoint blockade (ICB) immunotherapy has produced very significant advances in the fight against cancer (Figure 1). The synergistic combination of PD-1 and CTLA-4 blockade therapy has been successfully used

Immunometabolic cross-talk in the inflamed heart

Federica M. Marelli-Berg1,3 and Dunja Aksentijevic2,3

Inflammatory processes underlie many diseases associated with injury of the heart muscle, including conditions without an obvious inflammatory pathogenic component such as hypertensive and diabetic cardiomyopathy. Persistence of cardiac inflammation can cause irreversible structural and functional deficits. Some are induced by direct damage of the heart muscle by cellular and soluble mediators but also by metabolic adaptations sustained by the inflammatory microenvironment. It is well established that both cardiomyocytes and immune cells undergo metabolic reprogramming in the site of inflammation, which allow them to deal with decreased availability of nutrients and oxygen. However, like in cancer, competition for nutrients and increased production of signalling metabolites such as lactate initiate a metabolic cross-talk between immune cells and cardiomyocytes which, we propose, might tip the balance between resolution of the inflammation versus adverse cardiac remodeling. Here we review our current understanding of the metabolic reprogramming of both heart tissue and immune (...)

The role of epigenetics in hypothalamic energy balance control: implications for obesity

Arnaud Obri1 and Marc Claret1,2

INTRODUCTION The prevalence of obesity continues to increase worldwide. This trend is of concern because of its dramatic economic impact, concomitant decreased lifespan and increased comorbidities, such as hypertension, cardiovascular

Stress and catecholamines modulate the bone marrow microenvironment to promote tumorigenesis

Pauline Hanns1, Anna M. Paczulla1, Michael Medinger2, Martina Konantz1 and Claudia Lengerke1,2

High vascularization and locally secreted factors make the bone marrow (BM) microenvironment particularly hospitable for tumor cells and bones to a preferred metastatic site for disseminated cancer cells of different origins. Cancer cell homing and proliferation in the BM are amongst other regulated by complex interactions with BM niche cells (e.g. osteoblasts, endothelial cells and mesenchymal stromal cells (MSCs)), resident hematopoietic stem and progenitor cells (HSPCs) and pro-angiogenic cytokines leading to enhanced BM microvessel densities during malignant progression. Stress and catecholamine neurotransmitters released in response to activation of the sympathetic nervous system (SNS) reportedly modulate various BM cells and may thereby influence cancer progression. Here we review the role of catecholamines during tumorigenesis with particular focus on pro-tumorigenic effects mediated by the BM niche.

Remodeling of mitochondrial morphology and function: an emerging hallmark of cellular reprogramming

Anuj Rastogi1, Piyush Joshi2,3, Ela Contreras1 and Vivian Gama1,2,3,4

Research in the stem cell field has traditionally focused on understanding key transcriptional factors that provide pluripotent cell identity. However, much less is known about other critical non-transcriptional signaling networks that govern stem cell identity. Although we continue to gain critical insights into the mechanisms underlying mitochondrial morphology and function during cellular reprogramming – the process of reverting the fate of a differentiated cell into a stem cell, many uncertainties remain. Recent studies suggest an emerging landscape in which mitochondrial morphology and function have an active role in maintaining and regulating changes in cell identity. In this review, we will focus on these emerging concepts as crucial modulators of cellular reprogramming. Recognition of the widespread applicability of these concepts will increase our understanding of the mitochondrial mechanisms involved in cell identity, cell fate and disease.

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Regulation of T cell antitumor immune response by tumor induced metabolic stress

Fanny Chalmin1,2,3,4, Mélanie Bruchard1,2,3,4, Frederique Vegran1,2,3,4 and Francois Ghiringhelli1,2,3,4

Adaptive T cell immune response is essential for tumor growth control. The efficacy of immune checkpoint inhibitors is regulated by intratumoral immune response. The tumor microenvironment has a major role in adaptive immune response tuning. Tumor cells generate a particular metabolic environment in comparison to other tissues. Tumors are characterized by glycolysis, hypoxia, acidosis, amino acid depletion and fatty acid metabolism modification. Such metabolic changes promote tumor growth, impair immune response and lead to resistance to therapies. This review will detail how these modifications strongly affect CD8 and CD4 T cell functions and impact immunotherapy efficacy.

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LTX-315 – a promising novel antitumor peptide and immunotherapeutic agent

Dagmar Zweytick1,2

Host defense in mammals, as provided by the innate immune system, comprises proteins such as lactoferrin (LF), a multifunctional iron-binding glycoprotein originally discovered in bovine milk. LF is further pepsin-cleaved

Anti-regulatory T cells are natural regulatory effector T cells

Niels Ødum 1

It is well established that the immune system uses regulatory immune-suppressive cells to inhibit and terminate immune reactions and maintain immune balance. In the last decade, Andersen and colleagues have

The targeting of tumor-associated macrophages by vaccination

Mads Hald Andersen1,2,3

Immune suppressive myeloid cells include a heterogenous population of cells that include tumor-associated macrophages (TAMs). TAMs are major players in inducing the immunosuppressive microenvironment associated with many tumors. These lesions

Mitochondrial stress delays tumorigenesis in a Li-Fraumeni syndrome mouse model

Matthew P. Donnelly1, Jie Li1 and Paul M. Hwang1

As a prominent hub of metabolic activity, the mitochondrion can initiate retrograde signaling in response to bioenergetic stress that is important for various adaptive changes including cell cycle regulation [1][2].

Mitochondria organize the cellular proteostatic response and promote cellular senescence

Yanjun Li1, Lei Liu2, Yushan Zhu1 and Quan Chen1,2

Timely disposal and degradation of misfolded proteins and their aggregates is critical for cellular proteostasis and the well-being of a cell. During evolution, cells have acquired a sophisticated system to

Could de-stressing the brain be the solution for long-term weight loss?

Florian Seyfried1 and Mohammed K. Hankir2

INTRODUCTION One just needs to take a look at a typical vending machine (often found in hospitals) to appreciate what has happened to our food and drink. The relatively sudden