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Article ; Online: The Dutch well child language screening protocol for 2-year-old children was valid for detecting current and later language problems.

Visser-Bochane, Margot / Luinge, Margreet / Dieleman, Liesbeth / van der Schans, Cees / Reijneveld, Sijmen

Acta paediatrica (Oslo, Norway : 1992)

2020 Volume 110, Issue 2, Page(s) 556–562

Abstract: Aim: A little is known about predictive validity of and professionals' adherence to language screening protocols. This study assessed the concurrent and predictive validity of the Dutch well child language screening protocol for 2-year-old children and ... ...

Abstract	Aim: A little is known about predictive validity of and professionals' adherence to language screening protocols. This study assessed the concurrent and predictive validity of the Dutch well child language screening protocol for 2-year-old children and the effects of protocol deviations by professionals. Methods: A prospective cohort study of 124 children recruited and tested between October 2013 and December 2015. Children were recruited from four well child clinics in urban and rural areas. To validate the screening, we assessed children's language ability with standardised language tests following the 2-year screening and 1 year later. We assessed the concurrent and predictive validity of the screening and of protocol deviations. Results: At 2 years, the sensitivity and specificity of the language screening were 0.79 and 0.86, and at 3 years 0.82 and 0.74, respectively. Protocol deviations by professionals were rare (7%) and did not significantly affect the validity of the screening. Conclusion: The language screening protocol was valid for detecting current and later language problems. Deviations from the protocol by professionals were rare and did not affect the concurrent nor predictive validity of the protocol. The 2-year language screening supports professionals working in preventive child health care and deserves wider implementation in well child care.
MeSH term(s)	Child ; Child Language ; Child, Preschool ; Humans ; Language ; Language Tests ; Mass Screening ; Prospective Studies
Language	English
Publishing date	2020-07-07
Publishing country	Norway
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	203487-6
ISSN	1651-2227 ; 0365-1436 ; 0803-5253
ISSN (online)	1651-2227
ISSN	0365-1436 ; 0803-5253
DOI	10.1111/apa.15447
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Article ; Online: Motivations of patients and their care partners for visiting a memory clinic. A qualitative study.

Visser, Leonie N C / Fruijtier, Agnetha / Kunneman, Marleen / Bouwman, Femke H / Schoonenboom, Niki / Staekenborg, Salka S / Wind, Hilje A / Hempenius, Liesbeth / de Beer, Marlijn H / Roks, Gerwin / Boelaarts, Leo / Kleijer, Mariska / Smets, Ellen M A / van der Flier, Wiesje M

Patient education and counseling

2023 Volume 111, Page(s) 107693

Abstract: Objective: We investigated motivations of patients and care partners for their memory clinic visit, and whether these are expressed in consultations.: Methods: We included data from 115 patients (age 71 ± 11, 49% Female) and their care partners (N = ... ...

Abstract	Objective: We investigated motivations of patients and care partners for their memory clinic visit, and whether these are expressed in consultations. Methods: We included data from 115 patients (age 71 ± 11, 49% Female) and their care partners (N = 93), who completed questionnaires after their first consultation with a clinician. Audio-recordings of these consultations were available from 105 patients. Motivations for visiting the clinic were content-coded as reported by patients in the questionnaire, and expressed by patients and care partners in consultations. Results: Most patients reported seeking a cause for symptoms (61%) or to confirm/exclude a (dementia) diagnosis (16%), yet 19% reported another motivation: (more) information, care access, or treatment/advice. In the first consultation, about half of patients (52%) and care partners (62%) did not express their motivation(s). When both expressed a motivation, these differed in about half of dyads. A quarter of patients (23%) expressed a different/complementary motivation in the consultation, then reported in the questionnaire. Conclusion: Motivations for visiting a memory clinic can be specific and multifaceted, yet are often not addressed during consultations. Practice implications: We should encourage clinicians, patients, and care partners to talk about motivations for visiting the memory clinic, as a starting point to personalize (diagnostic) care.
MeSH term(s)	Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Male ; Motivation ; Caregivers ; Referral and Consultation ; Surveys and Questionnaires ; Ambulatory Care Facilities
Language	English
Publishing date	2023-03-03
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605590-4
ISSN	1873-5134 ; 0738-3991
ISSN (online)	1873-5134
ISSN	0738-3991
DOI	10.1016/j.pec.2023.107693
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Article: Rapid Response to Remdesivir in Hospitalised COVID-19 Patients: A Propensity Score Weighted Multicentre Cohort Study.

Infectious diseases and therapy

2023 Volume 12, Issue 10, Page(s) 2471–2484

Abstract: Introduction: Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients' respiratory insufficiency seemed to recover particularly rapidly after initiation of ... ...

Abstract	Introduction: Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients' respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir. Methods: This was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration. Results: Of 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79-1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48-1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (< 7 days) (OR 2.84, 95% CI 1.07-7.56). Conclusion: Remdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation.
Language	English
Publishing date	2023-10-06
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2701611-0
ISSN	2193-6382 ; 2193-8229
ISSN (online)	2193-6382
ISSN	2193-8229
DOI	10.1007/s40121-023-00874-2
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Article ; Online: Effect of switching from intermittently scanned to real-time continuous glucose monitoring in adults with type 1 diabetes: 24-month results from the randomised ALERTT1 trial.

Visser, Margaretha M / Charleer, Sara / Fieuws, Steffen / De Block, Christophe / Hilbrands, Robert / Van Huffel, Liesbeth / Maes, Toon / Vanhaverbeke, Gerd / Dirinck, Eveline / Myngheer, Nele / Vercammen, Chris / Nobels, Frank / Keymeulen, Bart / Mathieu, Chantal / Gillard, Pieter

The lancet. Diabetes & endocrinology

2023 Volume 11, Issue 2, Page(s) 96–108

Abstract: Background: Comparing Continuous With Flash Glucose Monitoring In Adults With Type 1 Diabetes (ALERTT1) examined whether switching from first-generation intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time continuous ... ...

Abstract	Background: Comparing Continuous With Flash Glucose Monitoring In Adults With Type 1 Diabetes (ALERTT1) examined whether switching from first-generation intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time continuous glucose monitoring (rtCGM) with alert functionality offers additional benefits to adults with type 1 diabetes. The extension of the randomised ALERTT1 trial assessed the effect of switching from isCGM to rtCGM up to 24 months. Methods: In this 6-month, double-arm, parallel-group, non-masked, randomised, controlled trial, done across six hospitals in Belgium, 254 adults aged 18 years or older with type 1 diabetes previously using isCGM were randomly assigned (1:1) to rtCGM with alerts (intervention; n=127) or isCGM without alerts (control; n=127). Upon completion of the 6-month trial, the control group switched to rtCGM (is-rtCGM group), and the intervention group continued rtCGM (rt-rtCGM group). The extension focused on within-group changes in time in range (TIR; 3·9-10·0 mmol/L; primary outcome), HbA Findings: 119 participants were assigned to the is-rtCGM group of whom 112 (94%) completed the 24-month trial, and 123 participants were assigned to the rt-rtCGM group of whom 117 (95%) completed the 24-month trial. TIR increased from 51·8% (95% CI 49·1-54·5) at start of rtCGM (month 6) to 63·5% (60·7-66·3) at month 12 in the is-rtCGM group, and remained stable up to month 24 (change 11·7 percentage points [pp] [9·4-14·0; p<0·0001). In the rt-rtCGM group, TIR increased from 52·5% (95% CI 49·8-55·1) at start of rtCGM (month 0) to 63·0% (60·3-65·8) at month 12, also remaining stable up to month 24 (change 10·5 pp [8·2-12·8]; p<0·0001). HbA Interpretation: Glycaemic control and hypoglycaemia worry improved significantly up to 24 months after switching from isCGM without alerts to rtCGM with alerts, supporting the use of rtCGM in the care of adults with type 1 diabetes. Funding: Dexcom.
MeSH term(s)	Humans ; Adult ; Diabetes Mellitus, Type 1/drug therapy ; Hypoglycemic Agents/therapeutic use ; Blood Glucose Self-Monitoring/methods ; Blood Glucose ; Hypoglycemia/prevention & control
Chemical Substances	Hypoglycemic Agents ; Blood Glucose
Language	English
Publishing date	2023-01-23
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2213-8595
ISSN (online)	2213-8595
DOI	10.1016/S2213-8587(22)00352-7
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Article ; Online: Recognition of cognitive dysfunction in hospitalised older patients: a flash mob study.

Visser, Fleur C W / van Eersel, Marlise E A / Hempenius, Liesbeth / Verwey, Nicolaas A / Band, Caterina / van der Bol, Jessica M / Boudestein, Kris / van Dijk, Suzanne C / Gobbens, Robbert / van der Hooft, Cornelis S / Kamper, Adriaan M / Ruiter, Rikje / Sipers, Walther / Spoelstra, Birgit N A / Stoffels, Josephine / Stolwijk-Woudstra, Dyane J / van Stralen, Karlijn J / van Strien, Astrid M / Wijngaarden, Marjolein A /

Winters, Marian / Strijkert, Fijanne / van Munster, Barbara C

BMC geriatrics

2024 Volume 24, Issue 1, Page(s) 66

Abstract: Background: It is important that healthcare professionals recognise cognitive dysfunction in hospitalised older patients in order to address associated care needs, such as enhanced involvement of relatives and extra cognitive and functional support. ... ...

Abstract	Background: It is important that healthcare professionals recognise cognitive dysfunction in hospitalised older patients in order to address associated care needs, such as enhanced involvement of relatives and extra cognitive and functional support. However, studies analysing medical records suggest that healthcare professionals have low awareness of cognitive dysfunction in hospitalised older patients. In this study, we investigated the prevalence of cognitive dysfunction in hospitalised older patients, the percentage of patients in which cognitive dysfunction was recognised by healthcare professionals, and which variables were associated with recognition. Methods: A multicentre, nationwide, cross-sectional observational study was conducted on a single day using a flash mob study design in thirteen university and general hospitals in the Netherlands. Cognitive function was assessed in hospitalised patients aged ≥ 65 years old, who were admitted to medical and surgical wards. A Mini-Cog score of < 3 out of 5 indicated cognitive dysfunction. The attending nurses and physicians were asked whether they suspected cognitive dysfunction in their patient. Variables associated with recognition of cognitive dysfunction were assessed using multilevel and multivariable logistic regression analyses. Results: 347 of 757 enrolled patients (46%) showed cognitive dysfunction. Cognitive dysfunction was recognised by attending nurses in 137 of 323 patients (42%) and by physicians in 156 patients (48%). In 135 patients (42%), cognitive dysfunction was not recognised by either the attending nurse or physician. Recognition of cognitive dysfunction was better at a lower Mini-Cog score, with the best recognition in patients with the lowest scores. Patients with a Mini-Cog score < 3 were best recognised in the geriatric department (69% by nurses and 72% by physicians). Conclusion: Cognitive dysfunction is common in hospitalised older patients and is poorly recognised by healthcare professionals. This study highlights the need to improve recognition of cognitive dysfunction in hospitalised older patients, particularly in individuals with less apparent cognitive dysfunction. The high proportion of older patients with cognitive dysfunction suggests that it may be beneficial to provide care tailored to cognitive dysfunction for all hospitalised older patients.
MeSH term(s)	Humans ; Aged ; Delirium ; Cross-Sectional Studies ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/epidemiology ; Cognitive Dysfunction/complications ; Patients ; Hospitalization
Language	English
Publishing date	2024-01-16
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/s12877-023-04588-5
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Article ; Online: Poor Outcome in Postpartum Breast Cancer Patients Is Associated with Distinct Molecular and Immunologic Features.

Lefrère, Hanne / Moore, Kat / Floris, Giuseppe / Sanders, Joyce / Seignette, Iris M / Bismeijer, Tycho / Peters, Dennis / Broeks, Annegien / Hooijberg, Erik / Van Calsteren, Kristel / Neven, Patrick / Warner, Ellen / Peccatori, Fedro Alessandro / Loibl, Sibylle / Maggen, Charlotte / Han, Sileny N / Jerzak, Katarzyna J / Annibali, Daniela / Lambrechts, Diether /

de Visser, Karin E / Wessels, Lodewyk / Lenaerts, Liesbeth / Amant, Frédéric

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 29, Issue 18, Page(s) 3729–3743

Abstract: Purpose: Patients with postpartum breast cancer diagnosed after cessation of breastfeeding (postweaning, PP-BCPW) have a particularly poor prognosis compared with patients diagnosed during lactation (PP-BCDL), or to pregnant (Pr-BC) and nulliparous (NP- ... ...

Abstract	Purpose: Patients with postpartum breast cancer diagnosed after cessation of breastfeeding (postweaning, PP-BCPW) have a particularly poor prognosis compared with patients diagnosed during lactation (PP-BCDL), or to pregnant (Pr-BC) and nulliparous (NP-BC) patients, regardless of standard prognostic characteristics. Animal studies point to a role of the involution process in stimulation of tumor growth in the mammary gland. However, in women, the molecular mechanisms that underlie this poor prognosis of patients with PP-BCPW remain vastly underexplored, due to of lack of adequate patient numbers and outcome data. Experimental design: We explored whether distinct prognostic features, common to all breast cancer molecular subtypes, exist in postpartum tumor tissue. Using detailed breastfeeding data, we delineated the postweaning period in PP-BC as a surrogate for mammary gland involution and performed whole transcriptome sequencing, immunohistochemical, and (multiplex) immunofluorescent analyses on tumor tissue of patients with PP-BCPW, PP-BCDL, Pr-BC, and NP-BC. Results: We found that patients with PP-BCPW having a low expression level of an immunoglobulin gene signature, but high infiltration of plasma B cells, have an increased risk for metastasis and death. Although PP-BCPW tumor tissue was also characterized by an increase in CD8+ cytotoxic T cells and reduced distance among these cell types, these parameters were not associated with differential clinical outcomes among groups. Conclusions: These data point to the importance of plasma B cells in the postweaning mammary tumor microenvironment regarding the poor prognosis of PP-BCPW patients. Future prospective and in-depth research needs to further explore the role of B-cell immunobiology in this specific group of young patients with breast cancer.
MeSH term(s)	Pregnancy ; Humans ; Animals ; Female ; Postpartum Period ; Lactation ; Prognosis ; Breast Neoplasms ; Tumor Microenvironment/genetics
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-22-3645
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Article ; Online: Methodological choices in experimental research on medical communication using vignettes: The impact of gender congruence and vignette modality.

Visser, Leonie N C / van der Velden, Naomi C A / Smets, Ellen M A / van der Lelie, Samantha / Nieuwenbroek, Eva / van Vliet, Liesbeth M / Hillen, Marij A

Patient education and counseling

2021 Volume 105, Issue 6, Page(s) 1634–1641

Abstract: Objective: Experimental vignette designs are used to systematically test the effects of medical communication. We tested the impact of two methodological choices -gender congruence and vignette modality- on analogue patient reported outcomes.: Methods! ...

Abstract	Objective: Experimental vignette designs are used to systematically test the effects of medical communication. We tested the impact of two methodological choices -gender congruence and vignette modality- on analogue patient reported outcomes. Methods: In an online experiment using a vignette portraying an oncological bad news consultation, we manipulated (1) gender congruence between the analogue and the vignette patient, and (2) vignette modality, i.e., text, audio, or video. Cancer-naïve students acting as analogue patients (N = 209, 22 ± 3 years old, 75% F) were assigned one randomly-selected vignette variant and completed questionnaires. Using 3 × 2 (repeated-measures) ANOVAs, we tested main and interaction effects of gender congruence and modality on self-reported engagement, recall, trust, satisfaction and anxiety. Results: We found no main effects of gender congruence or modality on any of the outcomes, nor any interaction effects between modality and congruence. Conclusion: Our results indicate that researchers may needlessly create gender-congruent vignettes at considerable cost and effort. Also, the currently assumed superiority of videos over other modalities for experimental vignette-based research may be inaccurate. Practice implications: Although further testing in an offline format and among different populations is warranted, decisions regarding gender congruence and modality for future vignette-based studies should be based primarily on their specific aims.
MeSH term(s)	Adult ; Communication ; Humans ; Physician-Patient Relations ; Referral and Consultation ; Surveys and Questionnaires ; Trust ; Young Adult
Language	English
Publishing date	2021-10-13
Publishing country	Ireland
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	605590-4
ISSN	1873-5134 ; 0738-3991
ISSN (online)	1873-5134
ISSN	0738-3991
DOI	10.1016/j.pec.2021.10.015
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Article ; Online: The Impact of Baseline User Characteristics on the Benefits of Real-Time Versus Intermittently Scanned Continuous Glucose Monitoring in Adults With Type 1 Diabetes: Moderator Analyses of the ALERTT1 Trial.

Visser, Margaretha Martha / Charleer, Sara / Fieuws, Steffen / De Block, Christophe / Hilbrands, Robert / Van Huffel, Liesbeth / Maes, Toon / Vanhaverbeke, Gerd / Dirinck, Eveline / Myngheer, Nele / Vercammen, Chris / Nobels, Frank / Keymeulen, Bart / Mathieu, Chantal / Gillard, Pieter

Journal of diabetes science and technology

2022 Volume 18, Issue 3, Page(s) 660–666

Abstract: Background: ALERTT1 showed that switching from intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time CGM (rtCGM) with alert functionality improved time in range (TIR; 70-180 mg/dL), glycated hemoglobin (HbA1c), time < ... ...

Abstract	Background: ALERTT1 showed that switching from intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time CGM (rtCGM) with alert functionality improved time in range (TIR; 70-180 mg/dL), glycated hemoglobin (HbA1c), time <54 mg/dL, and Hypoglycemia Fear Survey version II worry subscale (HFS-worry) score after six months in adults with type 1 diabetes (T1D). Moderator analyses aimed to identify certain subgroups that would benefit more from switching to rtCGM than others. Methods: Post hoc analyses of ALERTT1 evaluated the impact of 14 baseline characteristics on the difference (delta) in mean TIR, HbA1c, time <54 mg/dL, and HFS-worry score at six months between rtCGM and isCGM. Therefore, the delta was allowed to depend on each of these variables by including interactions in the moderator analysis model. Analyses were performed separately for each variable; variables with Results: Univariable analyses showed no dependency of delta TIR, HbA1c, or time <54 mg/dL on variables other than CGM type. Only delta HFS-worry score depended on baseline HbA1c ( Conclusions: Except for HFS-worry score, no interactions between 14 baseline characteristics and the six-month intervention effect of rtCGM on TIR, HbA1c, or time <54 mg/dL were observed, supporting the conclusion of ALERTT1 that switching from isCGM without alerts to rtCGM with alert functionality is beneficial for a wide range of people with T1D.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/drug therapy ; Blood Glucose Self-Monitoring/methods ; Adult ; Female ; Male ; Blood Glucose/analysis ; Glycated Hemoglobin/analysis ; Middle Aged ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/therapeutic use ; Insulin/administration & dosage ; Insulin/therapeutic use ; Insulin Infusion Systems ; Hypoglycemia/blood ; Hypoglycemia/chemically induced ; Hypoglycemia/prevention & control ; Hypoglycemia/diagnosis ; Glycemic Control ; Young Adult ; Continuous Glucose Monitoring
Chemical Substances	Blood Glucose ; Glycated Hemoglobin ; Hypoglycemic Agents ; Insulin ; hemoglobin A1c protein, human
Language	English
Publishing date	2022-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Randomized Controlled Trial ; Multicenter Study
ISSN	1932-2968
ISSN (online)	1932-2968
DOI	10.1177/19322968221128315
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Article ; Online: Body weight is negatively associated with direct oral anticoagulant trough concentrations in dabigatran and apixaban users.

Borst, Jacqueline M / van Rein, Nienke / Bakker, Emilie C M D / Vukadin, Nikola / Rier, Mike / Mairuhu, Albert T A / Hudig, Francisca / Bosma, Liesbeth B E / Wilms, Erik B / Visser, Loes E

British journal of haematology

2020 Volume 191, Issue 5, Page(s) 941–944

MeSH term(s)	Administration, Oral ; Aged ; Anticoagulants/administration & dosage ; Anticoagulants/adverse effects ; Body Weight ; Cross-Sectional Studies ; Dabigatran/administration & dosage ; Dabigatran/adverse effects ; Female ; Humans ; Male ; Pyrazoles/administration & dosage ; Pyrazoles/adverse effects ; Pyridones/administration & dosage ; Pyridones/adverse effects
Chemical Substances	Anticoagulants ; Pyrazoles ; Pyridones ; apixaban (3Z9Y7UWC1J) ; Dabigatran (I0VM4M70GC)
Language	English
Publishing date	2020-08-01
Publishing country	England
Document type	Clinical Trial ; Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.17009
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Article ; Online: Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness.

Lin, Chun-Pu / Levy, Pierre L / Alflen, Astrid / Apriamashvili, Georgi / Ligtenberg, Maarten A / Vredevoogd, David W / Bleijerveld, Onno B / Alkan, Ferhat / Malka, Yuval / Hoekman, Liesbeth / Markovits, Ettai / George, Austin / Traets, Joleen J H / Krijgsman, Oscar / van Vliet, Alex / Poźniak, Joanna / Pulido-Vicuña, Carlos Ariel / de Bruijn, Beaunelle / van Hal-van Veen, Susan E /

Boshuizen, Julia / van der Helm, Pim W / Díaz-Gómez, Judit / Warda, Hamdy / Behrens, Leonie M / Mardesic, Paula / Dehni, Bilal / Visser, Nils L / Marine, Jean-Christophe / Markel, Gal / Faller, William J / Altelaar, Maarten / Agami, Reuven / Besser, Michal J / Peeper, Daniel S

Cancer cell

2024 Volume 42, Issue 4, Page(s) 623–645.e10

Abstract: Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in ... ...

Abstract	Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 T cells to uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced cell death (AICD); (2) acute, triggering expansion; (3) chronic, causing dysfunction. Besides established regulators, we uncover genes controlling T cell fitness either specifically or commonly upon differential stimulation. Dap5 ablation, ranking highly in all three screens, increases translation while enhancing tumor killing. Loss of Icam1-mediated homotypic T cell clustering amplifies cell expansion and effector functions after both acute and intense stimulation. Lastly, Ctbp1 inactivation induces functional T cell persistence exclusively upon chronic stimulation. Our results functionally annotate fitness regulators based on their unique or shared contribution to traits limiting T cell antitumor activity.
MeSH term(s)	Humans ; CRISPR-Cas Systems ; CD8-Positive T-Lymphocytes ; Neoplasms/genetics
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2024.02.016
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In stock of ZB MED Cologne/Königswinter

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Full text online

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Order via subito

Inter-library loan at ZB MED

Full text online

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In stock of ZB MED Cologne/Königswinter

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More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito