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Article ; Online: Anti-PD-1 therapy triggers Tfh cell-dependent IL-4 release to boost CD8 T cell responses in tumor-draining lymph nodes.

Ruggiu, Mathilde / Guérin, Marion V / Corre, Béatrice / Bardou, Margot / Alonso, Ruby / Russo, Erica / Garcia, Zacarias / Feldmann, Lea / Lemaître, Fabrice / Dusseaux, Mathilde / Grandjean, Capucine L / Bousso, Philippe

The Journal of experimental medicine

2024 Volume 221, Issue 4

Abstract: Anti-PD-1 therapy targets intratumoral CD8+ T cells to promote clinical responses in cancer patients. Recent evidence suggests an additional activity in the periphery, but the underlying mechanism is unclear. Here, we show that anti-PD-1 mAb enhances CD8+ ...

Abstract	Anti-PD-1 therapy targets intratumoral CD8+ T cells to promote clinical responses in cancer patients. Recent evidence suggests an additional activity in the periphery, but the underlying mechanism is unclear. Here, we show that anti-PD-1 mAb enhances CD8+ T cell responses in tumor-draining lymph nodes by stimulating cytokine production in follicular helper T cells (Tfh). In two different models, anti-PD-1 mAb increased the activation and proliferation of tumor-specific T cells in lymph nodes. Surprisingly, anti-PD-1 mAb did not primarily target CD8+ T cells but instead stimulated IL-4 production by Tfh cells, the major population bound by anti-PD-1 mAb. Blocking IL-4 or inhibiting the Tfh master transcription factor BCL6 abrogated anti-PD-1 mAb activity in lymph nodes while injection of IL-4 complexes was sufficient to recapitulate anti-PD-1 mAb activity. A similar mechanism was observed in a vaccine model. Finally, nivolumab also boosted human Tfh cells in humanized mice. We propose that Tfh cells and IL-4 play a key role in the peripheral activity of anti-PD-1 mAb.
MeSH term(s)	Humans ; Mice ; Animals ; T Follicular Helper Cells ; T-Lymphocytes, Helper-Inducer ; Interleukin-4/metabolism ; Lymph Nodes ; Neoplasms/pathology ; CD8-Positive T-Lymphocytes
Chemical Substances	Interleukin-4 (207137-56-2)
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20232104
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Article ; Online: Tumor-intrinsic sensitivity to the pro-apoptotic effects of IFN-γ is a major determinant of CD4

Boulch, Morgane / Cazaux, Marine / Cuffel, Alexis / Guerin, Marion V / Garcia, Zacarias / Alonso, Ruby / Lemaître, Fabrice / Beer, Alexander / Corre, Béatrice / Menger, Laurie / Grandjean, Capucine L / Morin, Florence / Thieblemont, Catherine / Caillat-Zucman, Sophie / Bousso, Philippe

Nature cancer

2023 Volume 4, Issue 7, Page(s) 968–983

Abstract: ... ...

Abstract	CD4
MeSH term(s)	Humans ; Animals ; Mice ; T-Lymphocytes ; Receptors, Antigen, T-Cell ; Cytokines ; Interferon-gamma ; Neoplasms ; CD4-Positive T-Lymphocytes
Chemical Substances	Receptors, Antigen, T-Cell ; Cytokines ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2023-05-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-023-00570-7
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Article ; Online: Point-of-care ultrasound for tuberculosis diagnosis in children: a Médecins Sans Frontières cross-sectional study in Guinea-Bissau.

BMJ open

2023 Volume 13, Issue 5, Page(s) e066937

Abstract: Objective: Description of tuberculosis (TB)-focused point-of-care ultrasound (POCUS) findings for children with presumptive TB.: Design: Cross-sectional study (July 2019 to April 2020).: Setting: Simão Mendes hospital in Bissau, a setting with ... ...

Abstract	Objective: Description of tuberculosis (TB)-focused point-of-care ultrasound (POCUS) findings for children with presumptive TB. Design: Cross-sectional study (July 2019 to April 2020). Setting: Simão Mendes hospital in Bissau, a setting with high TB, HIV, and malnutrition burdens. Participants: Patients aged between 6 months and 15 years with presumptive TB. Interventions: Participants underwent clinical, laboratory and unblinded clinician-performed POCUS assessments, to assess subpleural nodules (SUNs), lung consolidation, pleural and pericardial effusion, abdominal lymphadenopathy, focal splenic and hepatic lesions and ascites. Presence of any sign prompted a POCUS positive result. Ultrasound images and clips were evaluated by expert reviewers and, in case of discordance, by a second reviewer. Children were categorised as confirmed TB (microbiological diagnosis), unconfirmed TB (clinical diagnosis) or unlikely TB. Ultrasound findings were analysed per TB category and risk factor: HIV co-infection, malnutrition and age. Results: A total of 139 children were enrolled, with 62 (45%) women and 55 (40%) aged <5 years; 83 (60%) and 59 (42%) were severely malnourished (SAM) and HIV-infected, respectively. TB confirmation occurred in 27 (19%); 62 (45%) had unconfirmed TB and 50 (36%) had unlikely TB. Children with TB were more likely to have POCUS-positive results (93%) compared with children with unlikely TB (34%). Common POCUS signs in patients with TB were: lung consolidation (57%), SUNs (55%) and pleural effusion (30%), and focal splenic lesions (28%). In children with confirmed TB, POCUS sensitivity was 85% (95% CI) (67.5% to 94.1%). In those with unlikely TB, specificity was 66% (95% CI 52.2% to 77.6%). Unlike HIV infection and age, SAM was associated with a higher POCUS-positivity. Cohen's kappa coefficient for concordance between field and expert reviewers ranged from 0.6 to 0.9. Conclusions: We found a high prevalence of POCUS signs in children with TB compared with children with unlikely TB. POCUS-positivity was dependent on nutritional status but not on HIV status or age. TB-focused POCUS could potentially play a supportive role in the diagnosis of TB in children. Trial registration number: NCT05364593.
MeSH term(s)	Humans ; Child ; Female ; Infant ; Male ; Cross-Sectional Studies ; HIV Infections/complications ; HIV Infections/epidemiology ; Point-of-Care Systems ; Guinea-Bissau ; Tuberculosis/diagnosis ; Ultrasonography/methods ; Malnutrition/diagnostic imaging ; Malnutrition/complications
Language	English
Publishing date	2023-05-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-066937
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Article ; Online: Numerical and clinical precision in hypoglycemia of the intermittent FreeStyle Libre glucose monitoring through an NFC-Bluetooth transmitter associated with the xDrip+ algorithm in diabetic patients under insulin therapy.

Gómez Medina, Ana María / Henao Carrillo, Diana Cristina / León Vargas, Fabian Mauricio / Jojoa Jojoa, Ruby Isabel / Quijano Naranjo, Jossie Esteban / Rondón-Sepulveda, Martin Alonso / García Jaramillo, Maira Alejandra / Muñoz Velandia, Oscar Mauricio

Endocrinologia, diabetes y nutricion

2023 Volume 70, Issue 3, Page(s) 212–219

Abstract: Introduction: There are data capture devices that attach to the FreeStyle Libre sensor and convert its communication from NFC (Near-field communication) to Bluetooth technology, generating real-time continuous glucose monitoring. The accuracy of ... ...

Abstract	Introduction: There are data capture devices that attach to the FreeStyle Libre sensor and convert its communication from NFC (Near-field communication) to Bluetooth technology, generating real-time continuous glucose monitoring. The accuracy of hypoglycemia measurements displayed by smartphone apps using this device has not been established. Methods: Study of diagnostic tests. Numerical accuracy was evaluated, utilizing the absolute difference with respect to capillary glucometry (ISO 15197:2015 standard) and clinical accuracy, using the Clarke and Parkes (Consensus) error grids, for glucose measurements less than 70mg/dL performed with the FreeStyle Libre system and with the digital estimation xDrip+ app, in diabetic patients managed with insulin therapy. Results: Twenty-seven patients were included (TIR 73.4%, TBR70 5.6%), who contributed 83 hypoglycemic events. Numerical accuracy was adequate in similar proportions with the FreeStyle Libre system compared to the xDrip+ app (81.92% vs. 68.67%, p=0.0630). The clinical accuracy evaluation showed that 92.8% of the measurements for xDrip+ and 98.8% for FreeStyle libre met the criteria according to the Parkes (Consensus) grid (p=0.0535); and 79.5% and 91.6% of the measurements met the criteria according to the Clarke grid (p=0.0273), being higher with FreeStyle libre. Conclusions: The use of the NFC-Bluetooth transmitter (Miao-Miao) associated with the xDrip+ app does not improve numerical or clinical accuracy for detecting hypoglycemic events in diabetic patients managed with insulin therapy, compared to the FreeStyle Libre device.
MeSH term(s)	Humans ; Insulin ; Blood Glucose Self-Monitoring ; Blood Glucose ; Diabetes Mellitus, Type 1/drug therapy ; Hypoglycemia/chemically induced ; Hypoglycemic Agents/adverse effects
Chemical Substances	Insulin ; Blood Glucose ; Hypoglycemic Agents
Language	English
Publishing date	2023-03-24
Publishing country	Spain
Document type	Journal Article
ISSN	2530-0180
ISSN (online)	2530-0180
DOI	10.1016/j.endien.2023.03.009
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Article ; Online: Aiming High: Monitoring Population Level Indicators of Child Wellbeing as a Goal of Community-Academic Partnerships.

Schmidt, Renae D / Armstrong, F Daniel / Horigian, Viviana E / Swilley-Woods, Graylyn / Alonso, Betty / Jackson, Douglene / Natale, Ruby / Jent, Jason / Schladant, Michelle / Nelson, Saliha / Brosco, Jeffrey P

Maternal and child health journal

2022 Volume 26, Issue 5, Page(s) 970–977

Abstract: Introduction: Community-academic partnerships (CAPs) aim to improve neighborhood population health. Though measuring the impact of partnership activities at a population level can be difficult, evaluating indicators of wellbeing may increase ... ...

Abstract	Introduction: Community-academic partnerships (CAPs) aim to improve neighborhood population health. Though measuring the impact of partnership activities at a population level can be difficult, evaluating indicators of wellbeing may increase understanding of how communities benefit from CAPs. This study examined child health indicators over time in two low-income, predominantly Black/African American and Hispanic communities where partnerships between an academic child development center and community coalitions were formed with the intention of improving child well-being. Methods: Trends in three child wellbeing indicators (graduation rates, kindergarten readiness, and proportion of youth in school and/or employed) were compared between two CAP communities and several neighboring comparison communities. Data between 2011 and 2017 were analyzed to calculate percent change from baseline and mapped using ArcGIS to visualize trends by zip code. Proportions of youth meeting benchmarks were also determined. Results: Kindergarten readiness and high-school graduation rates improved in CAP communities but not in geographically proximal and socioeconomically similar comparison communities. No improvements were found in the proportion of youth in school or employed. Discussion: This study revealed population-level indicators improved over time in CAP communities. Because community-level child health and wellbeing are influenced by many factors, this correlation is not proof of a causal relationship. Assessing population level indicators can nonetheless provide insight into the benefit of CAPs, and the commitment to monitoring such outcomes can itself advance how academic and community partners plan activities and set long-term goals.
MeSH term(s)	Adolescent ; Child ; Child Development ; Child Health ; Goals ; Humans ; Poverty ; Schools
Language	English
Publishing date	2022-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1339905-6
ISSN	1573-6628 ; 1092-7875
ISSN (online)	1573-6628
ISSN	1092-7875
DOI	10.1007/s10995-021-03333-x
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Article ; Online: Hepatitis C screening and detection program in a large population: Epidemiological transition and characterization of the disease.

Kershenobich, David / Higuera-de-la Tijera, Fatima / Flores, Nayelli / Cerda-Reyes, Eira / Castro-Narro, Graciela / Aceves, Guillermo / Ruiz-Lujan, Rodolfo / Ramos-Medina, Salvador / Linares, Jesus / Azamar-Alonso, Amilcar / Mendez-Navarro, Jorge / Chirino-Sprung, Ruby

Liver international : official journal of the International Association for the Study of the Liver

2023 Volume 43, Issue 6, Page(s) 1225–1233

Abstract: Introduction: Chronic hepatitis C (CHC) is considered an important public health challenge. Traditionally identified risk factors have undergone an epidemiological transition where other risk factors have become the main cause of new infections.: ... ...

Abstract	Introduction: Chronic hepatitis C (CHC) is considered an important public health challenge. Traditionally identified risk factors have undergone an epidemiological transition where other risk factors have become the main cause of new infections. Objective: To describe risk factors associated to hepatitis C positivity through the evaluation of the epidemiological profile in hepatitis-C high-risk populations. Methods: Cross-sectional study was conducted as part of an HCV screening program in Mexican population. All participants answered an HCV risk-factor questionnaire and took a rapid test (RT). All patients reactive to the test were subject to HCV PCR (polymerase chain reaction) confirmation. A logistic regression model was used to examine associations between HCV infection and risk factors. Results: The study included 297 631 participants that completed a risk factor questionnaire and underwent an HCV rapid test (RT). In total, 12 840 (4.5%) were reactive to RT and 9257 (3.2% of participants) were confirmed as positives by PCR test. Of these, 72.9% had at least one risk factor and 10.8% were in prison. Most common risk factors were history of acupuncture/tattooing/piercing (21%), intravenous drug use (15%) and high-risk sexual practices (12%). Logistic regressions found that having at least one risk factor increased the probability of having an HCV-positive result by 20% (OR = 1.20, 95% CI: 1.15-1.26), compared to the population without risk factors. Conclusions: We identified 3.2% of HCV-viremic subjects, all associated with risk factors and older age. Screening and diagnosis of HCV in high-risk populations (including underserved populations) should be more efficient.
MeSH term(s)	Humans ; Cross-Sectional Studies ; Hepatitis C/diagnosis ; Hepatitis C/epidemiology ; Hepatitis C/drug therapy ; Risk Factors ; Hepacivirus ; Substance Abuse, Intravenous/complications ; Prevalence
Language	English
Publishing date	2023-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2102783-3
ISSN	1478-3231 ; 1478-3223
ISSN (online)	1478-3231
ISSN	1478-3223
DOI	10.1111/liv.15570
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Article ; Online: Correction: Modeling the Specific CD4

Flament, Héloïse / Ramirez, Ruby Alonso / Prémel, Virginie / Joncker, Nathalie T / Jacquet, Alexandra / Scholl, Suzy / Lantz, Olivier

Journal of immunology (Baltimore, Md. : 1950)

2017 Volume 199, Issue 4, Page(s) 1526

Language	English
Publishing date	2017-08-15
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1700890
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Article ; Online: IL2/Anti-IL2 Complex Combined with CTLA-4, But Not PD-1, Blockade Rescues Antitumor NK Cell Function by Regulatory T-cell Modulation.

Caudana, Pamela / Núñez, Nicolas Gonzalo / De La Rochere, Philippe / Pinto, Anaïs / Denizeau, Jordan / Alonso, Ruby / Niborski, Leticia Laura / Lantz, Olivier / Sedlik, Christine / Piaggio, Eliane

Cancer immunology research

2019 Volume 7, Issue 3, Page(s) 443–457

Abstract: High-dose IL2 immunotherapy can induce long-lasting cancer regression but is toxic and insufficiently efficacious. Improvements are obtained with IL2/anti-IL2 complexes (IL2Cx), which redirect IL2 action to ... ...

Abstract	High-dose IL2 immunotherapy can induce long-lasting cancer regression but is toxic and insufficiently efficacious. Improvements are obtained with IL2/anti-IL2 complexes (IL2Cx), which redirect IL2 action to CD8
MeSH term(s)	Animals ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antigen-Antibody Complex/therapeutic use ; CD8-Positive T-Lymphocytes/immunology ; CTLA-4 Antigen/immunology ; Cell Line, Tumor ; Disease Models, Animal ; Drug Resistance, Neoplasm/drug effects ; Female ; Immunotherapy ; Interleukin-2/immunology ; Killer Cells, Natural/immunology ; Lymphocytes, Tumor-Infiltrating/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/therapy ; Programmed Cell Death 1 Receptor/immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Regulatory/immunology ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology
Chemical Substances	Antibodies, Monoclonal ; Antigen-Antibody Complex ; CTLA-4 Antigen ; Interleukin-2 ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2019-01-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-18-0697
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Article ; Online: Induction of anergic or regulatory tumor-specific CD4

Alonso, Ruby / Flament, Héloïse / Lemoine, Sébastien / Sedlik, Christine / Bottasso, Emanuel / Péguillet, Isabel / Prémel, Virginie / Denizeau, Jordan / Salou, Marion / Darbois, Aurélie / Núñez, Nicolás Gonzalo / Salomon, Benoit / Gross, David / Piaggio, Eliane / Lantz, Olivier

Nature communications

2018 Volume 9, Issue 1, Page(s) 2113

Abstract: ... ...

Abstract	CD4
MeSH term(s)	Adenocarcinoma of Lung/immunology ; Animals ; Antigens, Neoplasm/immunology ; Cell Differentiation/immunology ; Cell Line ; Clonal Anergy/immunology ; Disease Models, Animal ; Female ; HEK293 Cells ; Humans ; Immune Tolerance/immunology ; Lymph Nodes/cytology ; Lymph Nodes/immunology ; Lymphocyte Activation/immunology ; Mice ; Mice, Knockout ; T-Lymphocytes, Regulatory/immunology ; Tumor Escape/immunology
Chemical Substances	Antigens, Neoplasm
Language	English
Publishing date	2018-05-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-018-04524-x
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Article ; Online: A common transcriptomic program acquired in the thymus defines tissue residency of MAIT and NKT subsets.

Salou, Marion / Legoux, François / Gilet, Jules / Darbois, Aurélie / du Halgouet, Anastasia / Alonso, Ruby / Richer, Wilfrid / Goubet, Anne-Gaëlle / Daviaud, Céline / Menger, Laurie / Procopio, Emanuele / Premel, Virginie / Lantz, Olivier

The Journal of experimental medicine

2018 Volume 216, Issue 1, Page(s) 133–151

Abstract: Mucosal-associated invariant T (MAIT) cells are abundant T cells with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important functions, but their low frequency in mice has hampered their detailed ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are abundant T cells with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed the first transcriptomic analysis of murine MAIT cells. MAIT1 (RORγt
MeSH term(s)	Animals ; Female ; Humans ; Intercellular Adhesion Molecule-1/genetics ; Intercellular Adhesion Molecule-1/immunology ; Liver/immunology ; Liver/pathology ; Lung/immunology ; Lung/pathology ; Lymphocyte Function-Associated Antigen-1/genetics ; Lymphocyte Function-Associated Antigen-1/immunology ; Male ; Mice ; Mice, Transgenic ; Natural Killer T-Cells/immunology ; Natural Killer T-Cells/pathology ; Organ Specificity ; Spleen/immunology ; Spleen/pathology ; Thymus Gland/immunology ; Thymus Gland/pathology ; Transcriptome/immunology
Chemical Substances	ICAM1 protein, human ; Icam1 protein, mouse ; Lymphocyte Function-Associated Antigen-1 ; Intercellular Adhesion Molecule-1 (126547-89-5)
Language	English
Publishing date	2018-12-05
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20181483
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