Abstract:
:The search for non-invasive systemic biomarkers of response to PD-L1/PD-1 blockade immunotherapy is currently a priority in oncoimmunology. In contrast to classical tumor biomarkers, the identification of clinically useful immunological biomarkers is certainly a challenge, as anti-cancer immune responses depend on the coordinated action of many cell types. Studies on the dynamics of systemic CD8 T-cell populations have provided indications that such biomarkers may have a place in clinical practice. However, the power of CD8 T-cell subsets to discriminate clinical responses in immunotherapy has so far proven to be limited. The systemic evaluation of CD8 T-cell regulators such as myeloid cells and CD4 T cells may provide the solution. Here we discuss the value of systemic quantification of CD4 T-cell subsets for patient selection in light of the results obtained by Prof. Kagamu's and our team. Our studies have independently demonstrated that the evaluation of the pre-treatment status of systemic CD4 immunity is a critical factor for the clinical outcome of PD-L1/PD-1 blockade therapy with robust predictive capacities.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Zuazo M,Arasanz H,Bocanegra A,Chocarro L,Vera R,Escors D,Kagamu H,Kochan Gdoi
10.15252/emmm.202012706subject
Has Abstractpub_date
2020-09-07 00:00:00pages
e12706issue
9eissn
1757-4676issn
1757-4684journal_volume
12pub_type
杂志文章abstract::Secreted Semaphorin 3E (Sema3E) promotes cancer cell invasiveness and metastatic spreading. The pro-metastatic activity of Sema3E is due to its proteolytic fragment p61, capable of transactivating the oncogenic tyrosine kinase ErbB2 that associates with the Sema3E receptor PlexinD1 in cancer cells. Here, we show that ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100205
更新日期:2012-03-01 00:00:00
abstract::Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small-animal PET/MRI and the nove...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201506085
更新日期:2016-07-01 00:00:00
abstract::Mitochondrial metabolism and the generation of reactive oxygen species (ROS) contribute to the acquisition of DNA mutations and genomic instability in cancer. How genomic instability influences the metabolic capacity of cancer cells is nevertheless poorly understood. Here, we show that homologous recombination-defecti...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911217
更新日期:2020-06-08 00:00:00
abstract::Heart failure entails the inability of the heart to pump blood to vital organs. One of the main risk factors for heart failure is the development of pathological hypertrophy. In this issue of EMBO Molecular Medicine, Li and coworkers show that NCoR1, a co-repressor of transcription factors, inhibits the transcriptiona...
journal_title:EMBO molecular medicine
pub_type: 评论,杂志文章
doi:10.15252/emmm.201911297
更新日期:2019-11-07 00:00:00
abstract::The tumor suppressor gene TP53 is the most frequently mutated gene in cancer. The compound APR-246 (PRIMA-1Met/Eprenetapopt) is converted to methylene quinuclidinone (MQ) that targets mutant p53 protein and perturbs cellular antioxidant balance. APR-246 is currently tested in a phase III clinical trial in myelodysplas...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910852
更新日期:2020-12-14 00:00:00
abstract::There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells be...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404353
更新日期:2015-04-01 00:00:00
abstract::Muscle-invasive forms of urothelial carcinomas are responsible for most mortality in bladder cancer. Finding new treatments for invasive bladder tumours requires adequate animal models to decipher the mechanisms of progression, in particular the way tumours interact with their microenvironment. Herein, using the murin...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201302655
更新日期:2013-12-01 00:00:00
abstract::The prostate-specific membrane antigen (PSMA) has been demonstrated in numerous studies to be expressed specifically on prostate carcinoma cells and on the neovasculature of several other cancer entities. However, the simultaneous expression of PSMA on both, tumor cells as well as tumor vessels remains unclear, even i...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911902
更新日期:2020-12-29 00:00:00
abstract::Lipid droplets (LDs) are dynamic, cytosolic lipid-storage organelles found in nearly all cell types. Too many or too few LDs during excess or deficient fat storage lead to many different human diseases. Recent insights into LD biology and LD protein functions shed new light on mechanisms underlying those metabolic pat...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.1002/emmm.201100671
更新日期:2013-07-01 00:00:00
abstract::Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, which is characterized by cleft palate and severe defects of the skin, is an autosomal dominant disorder caused by mutations in the gene encoding transcription factor p63. Here, we report the generation of a knock-in mouse model for AEC syndrome (p63(...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100199
更新日期:2012-03-01 00:00:00
abstract::Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area com...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201506151
更新日期:2016-08-01 00:00:00
abstract::High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to ac...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910681
更新日期:2020-01-09 00:00:00
abstract::Fetal alcohol spectrum disorder (FASD) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal and Hsf2-deficient mice and cell systems to uncover a pivotal role for heat shock...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201303311
更新日期:2014-08-01 00:00:00
abstract::Candida albicans is a frequent aetiologic agent of sepsis associated with high mortality in immunocompromised patients. Developing new antifungal therapies is a medical need due to the low efficiency and resistance to current antifungal drugs. Here, we show that p38γ and p38δ regulate the innate immune response to C. ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201708485
更新日期:2018-05-01 00:00:00
abstract::Wnt/β-catenin signalling has been suggested to be active in basal-like breast cancer. However, in highly aggressive metastatic triple-negative breast cancers (TNBC) the role of β-catenin and the underlying mechanism(s) for the aggressiveness of TNBC remain unknown. We illustrate that WNT10B induces transcriptionally a...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201320
更新日期:2013-02-01 00:00:00
abstract::On November 14 last year, the British Guardian published an account from an anonymous whistleblower at Google, accusing the company of misconduct in regard to handling sensitive health data. The whistleblower works for Project Nightingale, an attempt by Google to get into the lucrative US healthcare market, by storing...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012053
更新日期:2020-03-06 00:00:00
abstract::The insulin/insulin-like growth factor-1 signalling (IIS) pathway regulates cellular and organismal metabolism and controls the rate of aging. Gain-of-function mutations in p110α, the principal mammalian IIS-responsive isoform of PI 3-kinase (PI3K), promote cancer. In contrast, loss-of-function mutations in p110α impa...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201953
更新日期:2013-04-01 00:00:00
abstract::Mutations in POLG disrupt mtDNA replication and cause devastating diseases often with neurological phenotypes. Defining disease mechanisms has been hampered by limited access to human tissues, particularly neurons. Using patient cells carrying POLG mutations, we generated iPSCs and then neural stem cells. These neural...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012146
更新日期:2020-10-07 00:00:00
abstract::Over thousands of years microbes and mammals have co-evolved, resulting in extraordinarily sophisticated molecular mechanisms permitting the organisms to survive together. Mycobacterium tuberculosis is one of the best examples of successful co-evolution, since the bacilli have infected one third of the human populatio...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.1002/emmm.200900008
更新日期:2009-04-01 00:00:00
abstract::Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201403943
更新日期:2014-06-01 00:00:00
abstract::Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests tha...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.15252/emmm.201607260
更新日期:2017-05-01 00:00:00
abstract::The cytokine TNF drives inflammatory diseases, e.g., Crohn's disease. In a mouse model of TNF-induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no longer protects in animals which l...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911917
更新日期:2020-10-07 00:00:00
abstract::Growing evidence supports that LKB1-deficient KRAS-driven lung tumors represent a unique therapeutic challenge, displaying strong cancer plasticity that promotes lineage conversion and drug resistance. Here we find that murine lung tumors from the KrasLSL-G12D/+ ; Lkb1flox/flox (KL) model show strong plasticity, which...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012627
更新日期:2021-01-13 00:00:00
abstract::Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target-agnostic approach based...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201808879
更新日期:2018-03-01 00:00:00
abstract::Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis a...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404883
更新日期:2015-04-01 00:00:00
abstract::Resistance to tamoxifen is a clinically major challenge in breast cancer treatment. Although downregulation of estrogen receptor-alpha (ERα) is the dominant mechanism of tamoxifen resistance, the reason for ERα decrease during tamoxifen therapy remains elusive. Herein, we reported that Spalt-like transcription factor ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910638
更新日期:2019-12-01 00:00:00
abstract::5'AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201302734
更新日期:2014-04-01 00:00:00
abstract::The current seasonal inactivated influenza vaccine protects only against a narrow range of virus strains as it triggers a dominant antibody response toward the hypervariable hemagglutinin (HA) head region. The discovery of rare broadly protective antibodies against conserved regions in influenza virus proteins has pro...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910938
更新日期:2020-05-08 00:00:00
abstract::The transcription factors of the MYC family play pivotal roles in the initiation and progression of human cancers. High oncogenic level of MYC invades low-affinity sites and enhancer sequences, which subsequently alters the transcriptome, causes metabolic imbalance, and induces stress response. The endoplasmic reticul...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.15252/emmm.201911845
更新日期:2020-05-08 00:00:00
abstract::KCNN3, encoding the small conductance calcium-activated potassium channel SK3, harbours a polymorphic CAG repeat in the amino-terminal coding region with yet unproven function. Hypothesizing that KCNN3 genotypes do not influence susceptibility to schizophrenia but modify its phenotype, we explored their contribution t...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100135
更新日期:2011-06-01 00:00:00