Volume 3 (2019)

Serum- and glucocorticoid-inducible kinase 1 and the response to cell stress

Florian Lang1, Christos Stournaras2, Nefeli Zacharopoulou2, Jakob Voelkl3,4, Ioana Alesutan3,4,5

INTRODUCTION The ubiquitously expressed [1][2][3][4] serum- and glucocorticoid-inducible kinase 1 (SGK1) has originally been cloned as a gene up-regulated by serum and glucocorticoids in rat mammary tumor cells [1][5]. The

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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The impact of endothelial cell death in the brain and its role after stroke: A systematic review

Marietta Zille1, Maulana Ikhsan1, Yun Jiang1,2, Josephine Lampe1,2, Jan Wenzel1,2 and
Markus Schwaninger1,2

INTRODUCTION The brain is a metabolically active organ that consumes about 20% of the total energy of the body [1]. At the same time, it is unable to store significant

Acyl-CoA-binding protein (ACBP): the elusive ‘hunger factor’ linking autophagy to food intake

José Manuel Bravo-San Pedro1-3, Valentina Sica1-3, Frank Madeo4,5 and Guido Kroemer1-3,6-8

Overweight has beaten undernutrition as the most frequent pathological state throughout the world, affecting close to 25% of the adult population. This has severe implications for global health, given that

Inflammation induced PD-L1-specific T cells

Shamaila Munir1, Mia Thorup Lundsager1, Mia Aabroe Jørgensen1, Morten Hansen1, Trine Hilkjær Petersen2, Charlotte Menne Bonefeld2, Christina Friese1, Özcan Met1,2, Per thor Straten1,2 and Mads Hald Andersen1,2,3

PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8+ and CD4+ T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-γ. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-γ generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in in vivo models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both (…)

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.

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The role of keratins in modulating carcinogenesis via communication with cells of the immune system

Inês Sequeira1 and Fiona M. Watt1

The connection between inflammation and cancer has been well established; however, little is known about the underlying mechanisms in the context of keratin loss. Keratins belong to a large family

Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response

Facundo Ramos1, María Teresa Villoria1, Esmeralda Alonso-Rodríguez1 and Andrés Clemente-Blanco1

INTRODUCTION Cells are constantly suffering endogenous and exogenous stresses that affect the integrity of the genetic material. It has been estimated that every cell of our body is exposed to

Hepatic stress associated with pathologies characterized by disturbed glucose production

Monika Gjorgjieva1-3,#, Gilles Mithieux1-3 and Fabienne Rajas1-3

LIVER FUNCTION IN GLUCOSE PRODUCTION AND NORMOGLYCEMIA Maintaining normal glucose levels in the organism i.e. between 0.7 to 1.1 g/L, is a complex task, involving a multi-organ crosstalk responsible for

Metabolic and functional reprogramming of myeloid-derived suppressor cells and their therapeutic control in glioblastoma

Woong-Jai Won1, Jessy S. Deshane2, Jianmei W. Leavenworth3, Claudia R. Oliva4 and Corinne E. Griguer4

Glioblastoma, also known as glioblastoma multiforme, is the most common and deadliest form of high-grade malignant brain tumors with limited available treatments. Within the glioblastoma tumor microenvironment (TME), tumor cells, stromal cells, and infiltrating immune cells continuously interact and exchange signals through various secreted factors including cytokines, chemokines, growth factors, and metabolites. Simultaneously, they dynamically reprogram their metabolism according to environmental energy demands such as hypoxia and neo-vascularization. Such metabolic reprogramming can determine fates and functions of tumor cells as well as immune cells. Ultimately, glioma cells in the TME transform immune cells to suppress anti-tumor immune cells such as T, natural killer (NK) cells, and dendritic cells (DC), and evade immune surveillance, and even to promote (...)

Development of novel methods that monitor necroptosis and the release of DAMPs at the single cell resolution

Hiroyasu Nakano1,2, Shin Murai1, Yoshifumi Yamaguchi3, Yoshitaka Shirasaki4,5, Osamu Nakabayashi1 and Soh Yamazaki1

HOW DOES SMART SENSE THE EXECUTION OF NECROPTOSIS? Various types of cells undergo necroptosis following stimulation with death ligands including tumor necrosis factor, Fas ligand, and TRAIL, or polyI:C, and

R-loops: formation, function, and relevance to cell stress

David F Allison1,2 and Gang Greg Wang1,2

INTRODUCTION A variety of topological, structural and hybridization events occur during DNA replication and gene transcription. Unwinding of the DNA double helix provides access for polymerase to a template strand,

P4HA1 is a new regulator of the HIF-1 pathway in breast cancer

Ren Xu1,2

Prolyl hydroxylation is a very common posttranslational protein modification. About 4% amino acid residues in animal proteins are hydroxyproline, and most of hydroxyproline is within collagen. Regulation of protein stability

Control of nucleolar stress and translational reprogramming by lncRNAs

Yvessa Verheyden1, Lucas Goedert1,2 and Eleonora Leucci1

INTRODUCTION Unfavourable environmental conditions trigger cellular responses that help minimize and/or repair the damage experienced by the cell. During stress responses, most of the biosynthetic processes of the cell are

Serum- and glucocorticoid-inducible kinase 1 and the response to cell stress

Florian Lang1, Christos Stournaras2, Nefeli Zacharopoulou2, Jakob Voelkl3,4, Ioana Alesutan3,4,5

INTRODUCTION The ubiquitously expressed [1][2][3][4] serum- and glucocorticoid-inducible kinase 1 (SGK1) has originally been cloned as a gene up-regulated by serum and glucocorticoids in rat mammary tumor cells [1][5]. The

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