Systemic CD4 immunity: A powerful clinical biomarker for PD-L1/PD-1 immunotherapy.

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 Med

journal_title

EMBO molecular medicine

authors

Zuazo M,Arasanz H,Bocanegra A,Chocarro L,Vera R,Escors D,Kagamu H,Kochan G

doi

10.15252/emmm.202012706

subject

Has Abstract

pub_date

2020-09-07 00:00:00

pages

e12706

issue

9

eissn

1757-4676

issn

1757-4684

journal_volume

12

pub_type

杂志文章
  • Tumour growth inhibition and anti-metastatic activity of a mutated furin-resistant Semaphorin 3E isoform.

    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

    authors: Casazza A,Kigel B,Maione F,Capparuccia L,Kessler O,Giraudo E,Mazzone M,Neufeld G,Tamagnone L

    更新日期:2012-03-01 00:00:00

  • A novel thermoregulatory role for PDE10A in mouse and human adipocytes.

    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

    authors: Hankir MK,Kranz M,Gnad T,Weiner J,Wagner S,Deuther-Conrad W,Bronisch F,Steinhoff K,Luthardt J,Klöting N,Hesse S,Seibyl JP,Sabri O,Heiker JT,Blüher M,Pfeifer A,Brust P,Fenske WK

    更新日期:2016-07-01 00:00:00

  • Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors.

    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

    authors: Lahiguera Á,Hyroššová P,Figueras A,Garzón D,Moreno R,Soto-Cerrato V,McNeish I,Serra V,Lazaro C,Barretina P,Brunet J,Menéndez J,Matias-Guiu X,Vidal A,Villanueva A,Taylor-Harding B,Tanaka H,Orsulic S,Junza A,Yanes O,

    更新日期:2020-06-08 00:00:00

  • Targeting cardiac hypertrophy through a nuclear co-repressor.

    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

    authors: Grund A,Heineke J

    更新日期:2019-11-07 00:00:00

  • A thiol-bound drug reservoir enhances APR-246-induced mutant p53 tumor cell death.

    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

    authors: Ceder S,Eriksson SE,Cheteh EH,Dawar S,Corrales Benitez M,Bykov VJN,Fujihara KM,Grandin M,Li X,Ramm S,Behrenbruch C,Simpson KJ,Hollande F,Abrahmsen L,Clemons NJ,Wiman KG

    更新日期:2020-12-14 00:00:00

  • A single epidermal stem cell strategy for safe ex vivo gene therapy.

    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

    authors: Droz-Georget Lathion S,Rochat A,Knott G,Recchia A,Martinet D,Benmohammed S,Grasset N,Zaffalon A,Besuchet Schmutz N,Savioz-Dayer E,Beckmann JS,Rougemont J,Mavilio F,Barrandon Y

    更新日期:2015-04-01 00:00:00

  • An essential role for decorin in bladder cancer invasiveness.

    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

    authors: El Behi M,Krumeich S,Lodillinsky C,Kamoun A,Tibaldi L,Sugano G,De Reynies A,Chapeaublanc E,Laplanche A,Lebret T,Allory Y,Radvanyi F,Lantz O,Eiján AM,Bernard-Pierrot I,Théry C

    更新日期:2013-12-01 00:00:00

  • An IgG-based bispecific antibody for improved dual targeting in PSMA-positive cancer.

    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

    authors: Zekri L,Vogt F,Osburg L,Müller S,Kauer J,Manz T,Pflügler M,Maurer A,Heitmann JS,Hagelstein I,Märklin M,Hörner S,Todenhöfer T,Calaminus C,Stenzl A,Pichler B,la Fougère C,Schneider MA,Rammensee HG,Zender L,Sipos B,

    更新日期:2020-12-29 00:00:00

  • Balancing the fat: lipid droplets and human disease.

    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

    authors: Krahmer N,Farese RV Jr,Walther TC

    更新日期:2013-07-01 00:00:00

  • Mutant p63 causes defective expansion of ectodermal progenitor cells and impaired FGF signalling in AEC syndrome.

    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

    authors: Ferone G,Thomason HA,Antonini D,De Rosa L,Hu B,Gemei M,Zhou H,Ambrosio R,Rice DP,Acampora D,van Bokhoven H,Del Vecchio L,Koster MI,Tadini G,Spencer-Dene B,Dixon M,Dixon J,Missero C

    更新日期:2012-03-01 00:00:00

  • Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture.

    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

    authors: Maruyama S,Nakamura K,Papanicolaou KN,Sano S,Shimizu I,Asaumi Y,van den Hoff MJ,Ouchi N,Recchia FA,Walsh K

    更新日期:2016-08-01 00:00:00

  • Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFβ.

    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

    authors: Germann M,Zangger N,Sauvain MO,Sempoux C,Bowler AD,Wirapati P,Kandalaft LE,Delorenzi M,Tejpar S,Coukos G,Radtke F

    更新日期:2020-01-09 00:00:00

  • Heat shock factor 2 is a stress-responsive mediator of neuronal migration defects in models of fetal alcohol syndrome.

    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

    authors: El Fatimy R,Miozzo F,Le Mouël A,Abane R,Schwendimann L,Sabéran-Djoneidi D,de Thonel A,Massaoudi I,Paslaru L,Hashimoto-Torii K,Christians E,Rakic P,Gressens P,Mezger V

    更新日期:2014-08-01 00:00:00

  • Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity.

    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

    authors: Alsina-Beauchamp D,Escós A,Fajardo P,González-Romero D,Díaz-Mora E,Risco A,Martín-Serrano MA,Del Fresno C,Dominguez-Andrés J,Aparicio N,Zur R,Shpiro N,Brown GD,Ardavín C,Netea MG,Alemany S,Sanz-Ezquerro JJ,Cuenda A

    更新日期:2018-05-01 00:00:00

  • WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer.

    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

    authors: Wend P,Runke S,Wend K,Anchondo B,Yesayan M,Jardon M,Hardie N,Loddenkemper C,Ulasov I,Lesniak MS,Wolsky R,Bentolila LA,Grant SG,Elashoff D,Lehr S,Latimer JJ,Bose S,Sattar H,Krum SA,Miranda-Carboni GA

    更新日期:2013-02-01 00:00:00

  • Google's Project Nightingale highlights the necessity of data science ethics review.

    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

    authors: Schneble CO,Elger BS,Shaw DM

    更新日期:2020-03-06 00:00:00

  • Long-term p110α PI3K inactivation exerts a beneficial effect on metabolism.

    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

    authors: Foukas LC,Bilanges B,Bettedi L,Pearce W,Ali K,Sancho S,Withers DJ,Vanhaesebroeck B

    更新日期:2013-04-01 00:00:00

  • Disease-specific phenotypes in iPSC-derived neural stem cells with POLG mutations.

    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

    authors: Liang KX,Kristiansen CK,Mostafavi S,Vatne GH,Zantingh GA,Kianian A,Tzoulis C,Høyland LE,Ziegler M,Perez RM,Furriol J,Zhang Z,Balafkan N,Hong Y,Siller R,Sullivan GJ,Bindoff LA

    更新日期:2020-10-07 00:00:00

  • Spotlight on Mycobacteria and dendritic cells: will novel targets to fight tuberculosis emerge?

    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

    authors: Mortellaro A,Robinson L,Ricciardi-Castagnoli P

    更新日期:2009-04-01 00:00:00

  • Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3.

    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

    authors: Khan NA,Auranen M,Paetau I,Pirinen E,Euro L,Forsström S,Pasila L,Velagapudi V,Carroll CJ,Auwerx J,Suomalainen A

    更新日期:2014-06-01 00:00:00

  • Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease.

    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

    authors: Holmberg FE,Seidelin JB,Yin X,Mead BE,Tong Z,Li Y,Karp JM,Nielsen OH

    更新日期:2017-05-01 00:00:00

  • Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium.

    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

    authors: Souffriau J,Timmermans S,Vanderhaeghen T,Wallaeys C,Van Looveren K,Aelbrecht L,Dewaele S,Vandewalle J,Goossens E,Verbanck S,Boyen F,Eggermont M,De Commer L,De Rycke R,De Bruyne M,Tito R,Ballegeer M,Vandevyver S,Velho

    更新日期:2020-10-07 00:00:00

  • Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation.

    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

    authors: Tong X,Chen Y,Zhu X,Ye Y,Xue Y,Wang R,Gao Y,Zhang W,Gao W,Xiao L,Chen H,Zhang P,Ji H

    更新日期:2021-01-13 00:00:00

  • Dissecting human antibody responses: useful, basic and surprising findings.

    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

    authors: Lanzavecchia A

    更新日期:2018-03-01 00:00:00

  • A streptococcal lipid toxin induces membrane permeabilization and pyroptosis leading to fetal injury.

    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

    authors: Whidbey C,Vornhagen J,Gendrin C,Boldenow E,Samson JM,Doering K,Ngo L,Ezekwe EA Jr,Gundlach JH,Elovitz MA,Liggitt D,Duncan JA,Adams Waldorf KM,Rajagopal L

    更新日期:2015-04-01 00:00:00

  • Epigenetic silencing of SALL2 confers tamoxifen resistance in breast cancer.

    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

    authors: Ye L,Lin C,Wang X,Li Q,Li Y,Wang M,Zhao Z,Wu X,Shi D,Xiao Y,Ren L,Jian Y,Yang M,Ou R,Deng G,Ouyang Y,Chen X,Li J,Song L

    更新日期:2019-12-01 00:00:00

  • A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis.

    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

    authors: Zadra G,Photopoulos C,Tyekucheva S,Heidari P,Weng QP,Fedele G,Liu H,Scaglia N,Priolo C,Sicinska E,Mahmood U,Signoretti S,Birnberg N,Loda M

    更新日期:2014-04-01 00:00:00

  • Adeno-associated virus-vectored influenza vaccine elicits neutralizing and Fcγ receptor-activating antibodies.

    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

    authors: Demminger DE,Walz L,Dietert K,Hoffmann H,Planz O,Gruber AD,von Messling V,Wolff T

    更新日期:2020-05-08 00:00:00

  • MYC and the unfolded protein response in cancer: synthetic lethal partners in crime?

    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

    authors: Zhang T,Li N,Sun C,Jin Y,Sheng X

    更新日期:2020-05-08 00:00:00

  • A CAG repeat polymorphism of KCNN3 predicts SK3 channel function and cognitive performance in schizophrenia.

    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

    authors: Grube S,Gerchen MF,Adamcio B,Pardo LA,Martin S,Malzahn D,Papiol S,Begemann M,Ribbe K,Friedrichs H,Radyushkin KA,Müller M,Benseler F,Riggert J,Falkai P,Bickeböller H,Nave KA,Brose N,Stühmer W,Ehrenreich H

    更新日期:2011-06-01 00:00:00