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Article ; Online: IL-15 boosts activated HBV core-specific CD8+ progenitor cells via metabolic rebalancing in persistent HBV infection

Julia Peña-Asensio / Henar Calvo-Sánchez / Joaquín Miquel / Eduardo Sanz-de-Villalobos / Alejandro González-Praetorius / Miguel Torralba / Juan-Ramón Larrubia

iScience, Vol 27, Iss 1, Pp 108666- (2024)

1481

Abstract: Summary: A rebalance between energy supply and demand in HBV-specific-CD8+ activated progenitor (AP) cells could restore the functionality of proliferative progeny (PP) in e-antigen(Ag)-negative chronic hepatitis B (CHBe(−)). We observed that quiescent ... ...

Abstract	Summary: A rebalance between energy supply and demand in HBV-specific-CD8+ activated progenitor (AP) cells could restore the functionality of proliferative progeny (PP) in e-antigen(Ag)-negative chronic hepatitis B (CHBe(−)). We observed that quiescent progenitor (QP [TCF1+/FSClow]) HBVcore-specific-CD8+ cells displayed a memory-like phenotype. Following Ag-encounter, the generated AP [TCF1+/FSChigh] subset maintained the PD1+/CD127+ phenotype and gave rise to proliferative progeny (PP [ TCF1-/FSChigh]). In AP cells, IL-15 compared to IL2 decreased the initial mTORC1 boost, but maintained its activation longer linked to a catabolic profile that correlated with enhanced PP effector abilities. In nucleos(t)ide analogue (NUC)-treated CHBe(−), AP subset showed an anabolic phenotype associated with a dysfunctional PP pool. In CHBe(−) cases with low probability of HBVcore-specific-CD8+ cell on-NUC-treatment restoration, according to a clinical predictive model, IL-15/anti-PD-L1 treatment re-established their reactivity. Therefore, IL-15 could improve AP pool energy balance by decreasing intensity but extending T cell activation and by inducing a more catabolic metabolism.
Keywords	Biological sciences ; Microbiology ; Virology ; Science ; Q
Subject code	570
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: IL-15 boosts activated HBV core-specific CD8

Peña-Asensio, Julia / Calvo-Sánchez, Henar / Miquel, Joaquín / Sanz-de-Villalobos, Eduardo / González-Praetorius, Alejandro / Torralba, Miguel / Larrubia, Juan-Ramón

iScience

2023 Volume 27, Issue 1, Page(s) 108666

Abstract: A rebalance between energy supply and demand in HBV-specific- ... ...

Abstract	A rebalance between energy supply and demand in HBV-specific-CD8
Language	English
Publishing date	2023-12-07
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108666
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Book ; Online: Pulse-Width Modulation Technique With Harmonic Injection in the Modulating Wave and Discontinuous Frequency Modulation for the Carrier Wave for Multilevel Inverters

Ruiz-Gonzalez, Antonio / Heredia-Larrubia, Juan-Ramon / Meco-Gutierrez, Mario J. / Perez-Hidalgo, Francisco-M.

An Application to the Reduction of Acoustic Noise in Induction Motors

2024

Abstract: An implementation of a harmonic injection pulse width modulation frequency-modulated triangular carrier (HIPWM-FMTC) control strategy applied to a multilevel power inverter feeding an asynchronous motor is presented. The aim was to justify the reduction ... ...

Abstract	An implementation of a harmonic injection pulse width modulation frequency-modulated triangular carrier (HIPWM-FMTC) control strategy applied to a multilevel power inverter feeding an asynchronous motor is presented. The aim was to justify the reduction in acoustic noise emitted by the machine compared with other strategies in the technical literature. In addition, we checked how the THD at the inverter output was reduced compared to the other control techniques used as a reference. The proposed strategy is based on frequency modulation of the triangular carrier. The main advantage of the proposed method is that only one control parameter is required for modifying the electrical spectrum. Therefore, the mechanical natural frequencies and spatial harmonics of the machine can be avoided, and acoustic noise can be reduced. The effectiveness of the technique was demonstrated after laboratory validation by comparing the acoustic results for a 1 kW motor. The results obtained from the laboratory tests are presented and compared with those of other acoustic measurements using different PWM strategies.
Keywords	Electrical Engineering and Systems Science - Systems and Control
Subject code	600
Publishing date	2024-01-27
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: HBsAg level defines different clinical phenotypes of HBeAg(-) chronic HBV infection related to HBV polymerase-specific CD8

Peña-Asensio, Julia / Calvo-Sánchez, Henar / Miquel-Plaza, Joaquín / Sanz-de-Villalobos, Eduardo / González-Praetorius, Alejandro / Delgado-Fernandez, Alberto / Torralba, Miguel / Larrubia, Juan-Ramón

Frontiers in immunology

2024 Volume 15, Page(s) 1352929

Abstract: Background: HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8: Aims: To assess whether HBsAg level could discriminate different HBeAg-negative ... ...

Abstract	Background: HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8 Aims: To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8 Methods: We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8 Results: A positive linear trend between HBsAg level and APRI, liver stiffness (LS), liver transaminases, and HBV VL, and a negative correlation with platelet count were observed. Frequency of cases with HBV-specific CD8 Conclusion: HBsAg > 1,000 IU/ml HBeAg-negative chronic HBV infection group shows indirect data of higher degree of inflammation, liver stiffness, and fibrosis progression speed, which are related to an impaired HBV-polymerase-specific CD8
MeSH term(s)	Humans ; Hepatitis B, Chronic ; Hepatitis B virus/physiology ; Hepatitis B Surface Antigens/genetics ; Hepatitis B e Antigens/genetics ; Inflammation ; Liver Cirrhosis ; CD8-Positive T-Lymphocytes ; Alanine Transaminase ; Phenotype ; Gene Products, pol
Chemical Substances	Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; P protein, Hepatitis B virus ; Alanine Transaminase (EC 2.6.1.2) ; Gene Products, pol
Language	English
Publishing date	2024-03-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1352929
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Article ; Online: Letter: the probability to predict HBV-specific CD8+ cell response derived from HLA-A2+ may not foresee the functional cure well in Asian off-therapy cohort-authors' reply.

Peña-Asensio, Julia / Calvo, Henar / Miquel, Joaquín / Sanz-de-Villalobos, Eduardo / González-Praetorius, Alejandro / Torralba, Miguel / Larrubia, Juan-Ramón

Alimentary pharmacology & therapeutics

2022 Volume 56, Issue 8, Page(s) 1312–1313

MeSH term(s)	CD8-Positive T-Lymphocytes ; Cohort Studies ; HLA-A2 Antigen ; Hepatitis B virus/genetics ; Humans ; Probability
Chemical Substances	HLA-A2 Antigen
Language	English
Publishing date	2022-09-24
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.17212
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Article: A new year and a new roadmap for the journal in challenging times.

Fernandez Rodriguez, Conrado M / Larrubia Marfil, Juan Ramón

Revista espanola de enfermedades digestivas

2023 Volume 115, Issue 1, Page(s) 1–2

Abstract: ... later, in November 2021, Dr Juan-Ramon Larrubia joined the journal as Executive Editor. We thank ...

Abstract	Sixteen months have passed since I had the honor of being appointed editor-in-chief of Revista Española de Enfermedades Digestivas (The Spanish Journal of Gastroenterology) (REED) and thank the Spanish Society of Digestive Diseases (SEPD) for trusting me in this new phase of the REED history. Four months later, in November 2021, Dr Juan-Ramon Larrubia joined the journal as Executive Editor. We thank the former Editor-in-Chief and deputy-editor Enrique Peéez-Cuadrado and Javier A. Cienfuegos, respectively, their devoted work putting the journal on an upward trajectory since 2016, one year before the REED centenary, they set the bar very high.
MeSH term(s)	Humans ; Gastroenterology ; Digestive System Diseases ; Spain
Language	English
Publishing date	2023-02-01
Publishing country	Spain
Document type	Journal Article
ZDB-ID	1070381-0
ISSN	1130-0108 ; 0212-7512
ISSN	1130-0108 ; 0212-7512
DOI	10.17235/reed.2022.9372/2022
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Article ; Online: Model to predict on-treatment restoration of functional HBV-specific CD8

Peña-Asensio, Julia / Calvo, Henar / Miquel, Joaquín / Sanz-de-Villalobos, Eduardo / González-Praetorius, Alejandro / Torralba, Miguel / Larrubia, Juan-Ramón

Alimentary pharmacology & therapeutics

2022 Volume 55, Issue 12, Page(s) 1545–1559

Abstract: Background: Hepatitis B virus (HBV)-specific CD8: Aim: To predict this response with variables involved in T-cell exhaustion for use as a treatment stopping tool.: Methods: In NUC-treated CHBe(-) patients, we considered a functional response in ... ...

Abstract	Background: Hepatitis B virus (HBV)-specific CD8 Aim: To predict this response with variables involved in T-cell exhaustion for use as a treatment stopping tool. Methods: In NUC-treated CHBe(-) patients, we considered a functional response in cases with HBV-specific CD8 Results: We developed an LRM that predicted the presence of a proliferative type I cytokine-secreting CD8 Conclusions: Short-term low-level antigen exposure and early long-term NUC treatment influence the restoration of a functional HBV-specific CD8
MeSH term(s)	Adult ; Antiviral Agents/therapeutic use ; CD8-Positive T-Lymphocytes ; Cytokines ; DNA, Viral/genetics ; Epitopes ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Hepatitis B virus/genetics ; Hepatitis B, Chronic ; Humans ; Treatment Outcome
Chemical Substances	Antiviral Agents ; Cytokines ; DNA, Viral ; Epitopes ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens
Language	English
Publishing date	2022-02-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.16850
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Article ; Online: Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8 + T Cell Response during Chronic Hepatitis C

Julia Peña-Asensio / Henar Calvo / Miguel Torralba / Joaquín Miquel / Eduardo Sanz-de-Villalobos / Juan-Ramón Larrubia

Cells, Vol 10, Iss 538, p

2021 Volume 538

Abstract: Hepatitis C virus (HCV)-specific CD8 + T cell response is essential in natural HCV infection control, but it becomes exhausted during persistent infection. Nowadays, chronic HCV infection can be resolved by direct acting anti-viral treatment, but there ... ...

Abstract	Hepatitis C virus (HCV)-specific CD8 + T cell response is essential in natural HCV infection control, but it becomes exhausted during persistent infection. Nowadays, chronic HCV infection can be resolved by direct acting anti-viral treatment, but there are still some non-responders that could benefit from CD8 + T cell response restoration. To become fully reactive, T cell needs the complete release of T cell receptor (TCR) signalling but, during exhaustion this is blocked by the PD-1 effect on CD28 triggering. The T cell pool sensitive to PD-1 modulation is the progenitor subset but not the terminally differentiated effector population. Nevertheless, the blockade of PD-1/PD-L1 checkpoint cannot be always enough to restore this pool. This is due to the HCV ability to impair other co-stimulatory mechanisms and metabolic pathways and to induce a pro-apoptotic state besides the TCR signalling impairment. In this sense, gamma-chain receptor cytokines involved in memory generation and maintenance, such as low-level IL-2, IL-7, IL-15, and IL-21, might carry out a positive effect on metabolic reprogramming, apoptosis blockade and restoration of co-stimulatory signalling. This review sheds light on the role of combinatory immunotherapeutic strategies to restore a reactive anti-HCV T cell response based on the mixture of PD-1 blocking plus IL-2/IL-7/IL-15/IL-21 treatment.
Keywords	Hepatitis C virus ; CD8 + T cell response ; exhaustion ; immune checkpoints ; γ-chain cytokines ; PD-1 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8

Peña-Asensio, Julia / Calvo, Henar / Torralba, Miguel / Miquel, Joaquín / Sanz-de-Villalobos, Eduardo / Larrubia, Juan-Ramón

Cancers

2021 Volume 13, Issue 8

Abstract: Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either ... ...

Abstract	Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens or aberrantly expressed host's antigens, but they become progressively exhausted or deleted. These cells express the negative immunoregulatory checkpoint programmed cell death protein 1 (PD-1) which impairs T cell receptor signaling by blocking the CD28 positive co-stimulatory signal. The pool of CD8 cells sensitive to anti-PD-1/PD-L1 treatment is the PD-1dim memory-like precursor pool that gives rise to the effector subset involved in HCC control. Due to the epigenetic imprints that are transmitted to the next generation, the effect of PD-1 blockade is transient, and repeated treatments lead to tumor resistance. During long-lasting disease, besides the TCR signaling impairment, T cells develop other failures that should be also set-up to increase T cell reactivity. Therefore, several PD-1 blockade-based combinatory therapies are currently under investigation such as adding antiangiogenics, anti-TGFβ1, blockade of other negative immune checkpoints, or increasing HCC antigen presentation. The effect of these combinations on CD8
Language	English
Publishing date	2021-04-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13081922
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Article ; Online: Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8

Peña-Asensio, Julia / Calvo, Henar / Torralba, Miguel / Miquel, Joaquín / Sanz-de-Villalobos, Eduardo / Larrubia, Juan-Ramón

Cells

2021 Volume 10, Issue 3

Abstract: Hepatitis C virus (HCV)-specific ... ...

Abstract	Hepatitis C virus (HCV)-specific CD8
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/genetics ; B7-H1 Antigen/immunology ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/virology ; Gene Expression Regulation ; Hepacivirus/immunology ; Hepacivirus/pathogenicity ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/immunology ; Hepatitis C, Chronic/virology ; Host-Pathogen Interactions/drug effects ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunity, Cellular/drug effects ; Immunotherapy/methods ; Interleukins/genetics ; Interleukins/immunology ; Interleukins/therapeutic use ; Lymphocyte Activation/drug effects ; Precursor Cells, T-Lymphoid/drug effects ; Precursor Cells, T-Lymphoid/immunology ; Precursor Cells, T-Lymphoid/virology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/immunology ; Receptors, Antigen, T-Cell, gamma-delta/agonists ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Signal Transduction
Chemical Substances	Antibodies, Monoclonal ; B7-H1 Antigen ; CD274 protein, human ; Immune Checkpoint Inhibitors ; Interleukins ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2021-03-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10030538
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