| 1. |
- Kruse, Bastian, et al.
(author)
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CD4+ T cell-induced inflammatory cell death controls immune-evasive tumours
- 2023
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 618:7967, s. 1033-1040
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Journal article (peer-reviewed)abstract
- Most clinically applied cancer immunotherapies rely on the ability of CD8+ cytolytic T cells to directly recognize and kill tumour cells1,2,3. These strategies are limited by the emergence of major histocompatibility complex (MHC)-deficient tumour cells and the formation of an immunosuppressive tumour microenvironment4,5,6. The ability of CD4+ effector cells to contribute to antitumour immunity independently of CD8+ T cells is increasingly recognized, but strategies to unleash their full potential remain to be identified7,8,9,10. Here, we describe a mechanism whereby a small number of CD4+ T cells is sufficient to eradicate MHC-deficient tumours that escape direct CD8+ T cell targeting. The CD4+ effector T cells preferentially cluster at tumour invasive margins where they interact with MHC-II+CD11c+ antigen-presenting cells. We show that T helper type 1 cell-directed CD4+ T cells and innate immune stimulation reprogramme the tumour-associated myeloid cell network towards interferon-activated antigen-presenting and iNOS-expressing tumouricidal effector phenotypes. Together, CD4+ T cells and tumouricidal myeloid cells orchestrate the induction of remote inflammatory cell death that indirectly eradicates interferon-unresponsive and MHC-deficient tumours. These results warrant the clinical exploitation of this ability of CD4+ T cells and innate immune stimulators in a strategy to complement the direct cytolytic activity of CD8+ T cells and natural killer cells and advance cancer immunotherapies.
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| 2. |
- Oksuzyan, Anna, et al.
(author)
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Is Who you Ask Important? Concordance Between Survey and Registry Data on Medication Use Among Self- and Proxy-Respondents in the Longitudinal Study of Aging Danish Twins and the Danish 1905-Cohort Study
- 2019
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 74:5, s. 742-747
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Journal article (peer-reviewed)abstract
- Background: This study investigates the accuracy of the reporting of medication use by proxy-and self-respondents, and it compares the prognostic value of the number of medications from survey and registry data for predicting mortality across self-and proxy-respondents.Methods: The study is based on the linkage of the Longitudinal Study of Aging Danish Twins and the Danish 1905-Cohort Study with the Danish National Prescription Registry. We investigated the concordance between survey and registry data, and the prognostic value of medication use when assessed using survey and registry data, to predict mortality for self-and proxy-respondents at intake surveys.Results: Among self-respondents, the agreement was moderate (kappa = 0.52-0.58) for most therapeutic groups, whereas among proxy-respondents, the agreement was low to moderate (kappa = 0.36-0.60). The magnitude of the relative differences was, generally, greater among proxies than among self-respondents. Each additional increase in the total number of medications was associated with 7%-8% mortality increase among self- and 4%-6% mortality increase among proxy-respondents in both the survey and registry data. The predictive value of the total number of medications estimated from either data source was lower among proxies (c-statistic = 0.56-0.58) than among self-respondents (c-statistic = 0.74).Conclusions: The concordance between survey and registry data regarding medication use and the predictive value of the number of medications for mortality were lower among proxy-than among self-respondents.
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| 3. |
- Santacroce, Adriana, et al.
(author)
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Gender differences in the use of anti-infective medications before and after widowhood : a register-based study
- 2018
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In: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 72:6, s. 526-531
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Journal article (peer-reviewed)abstract
- Background Recent findings suggest that bereavement due to spousal loss is associated with a decline in general immune functions, and thus to increased susceptibility to infections among widowed individuals. The present study aims to investigate whether spousal loss weakens immune defences more among men than among women using a 5% random sample of the total Danish population, and anti-infective medication use as a proxy for immune response.Methods We followed 6076 Danish individuals (67% women) aged 50 from 5years before and up to 5years after widowhood to examine changes in prescriptions of anti-infectives for systemic use.Results Women used more anti-infective drugs both before and after spousal loss (women: OR= 1.31; 95% CI 1.21 to 1.42). The age-related changes in the use of anti-infective medications in the period before widowhood were similar to that in the period after widowhood among both men and women. Also, age-related changes in the use of anti-infective medications were similar in both genders.Conclusions The present study shows that individuals are more likely to use anti-infective medication after being widowed than before being widowed, but this change is likely to be related to increasing age and it is similar in both genders.
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