Functional immune reconstitution early after allogeneic haematopoietic cell transplantation: A comparison of pre‐ and post‐transplantation cytokine responses in stimulated whole blood

Gjærde, Lars Klingen; Brooks, Patrick Terrence; Andersen, Niels Smedegaard; Friis, Lone Smidstrup; Kornblit, Brian; Petersen, Solveig; Schjødt, Ida; Nielsen, Susanne Dam; Ostrowski, Sisse Rye; Sengeløv, Henrik

doi:10.1111/sji.13042

Cited by 10 publications

(15 citation statements)

References 45 publications

(77 reference statements)

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“…In the present study, we found monocyte counts to be associated with stimulated and unstimulated IL-8 and IL-6 release, emphasizing the potential critical role of these signaling molecules for differentiation of monocytes (IL-8) to macrophages (IL-8 and IL-6). As we found neither granulocytes nor other leukocyte subtypes to be associated with neither stimulated nor unstimulated TruCulture ® cytokine release, our results are in accordance with those by Gjaerde et al (27), namely that TruCulture ® may reveal an improved function of the immune cells and not simply increased immune cells in cancer patients. However, it should be emphasized that our study and hence results are explorative and needs confirmation in larger data sets.…”

Section: Discussionsupporting

confidence: 92%

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

et al. 2022

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IntroductionThe immune system has proven to be a key player in the progression as well as containment of cancer with new treatment strategies based on immunotherapy targeting this interaction. Assessing immune function could reveal critical information about the immune response to therapeutic interventions, revealing predictive biomarkers for tailored care and precision medicine.MethodsWe investigated immune function in 37 patients with inoperable non-small cell lung cancer (NSCLC) undergoing treatment with PD-L1 immune checkpoint inhibitor (ICI), chemotherapy (CT) or chemo-radiotherapy (CT/RT). Blood samples before (day 0) and during therapy (day 7, 21 and 80) were investigated by a standardized immunoassay, TruCulture®.ResultsOutcomes revealed a developing innate immune response induced by both immunotherapy and chemotherapy. NSCLC-patients displayed evidence of chronic innate immune activation and exhaustion prior to treatment. This pattern was particularly pronounced during treatment in patients dying within 12-months follow-up. Compared to treatment with CT, ICI demonstrated a higher ex vivo-stimulated release of proinflammatory cytokines.DiscussionThese preliminary findings may pave the way for tailored treatment and immune-monitoring.

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Section: Discussionsupporting

confidence: 92%

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

et al. 2022

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“…The shift from highly positive intercorrelations of induced cytokines in the LPS- and R848-induced samples before cART to less and more diverse intercorrelations have been described in another study using the TruCulture ® technique in patients with hematological diseases undergoing allogeneic hematopoietic stem cell transplantation with subsequent immune reconstruction ( 45 ). However, the mechanism behind the different cytokine correlations before and after immune reconstruction remains unclear.…”

Section: Discussionmentioning

confidence: 71%

Improved induced innate immune response after cART initiation in people with HIV

et al. 2022

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IntroductionImpairment of the innate immune function may contribute to the increased risk of bacterial and viral infections in people with HIV (PWH). In this study we aimed to investigate the induced innate immune responses in PWH prior to and after initiation of combinational antiretroviral therapy (cART). Furthermore, we aimed to investigate if the induced innate immune responses before initiation of cART were associated with CD4+ T-cell recovery one year after initiating cART.Material and methodThe induced innate immune response was assessed by the TruCulture® whole blood technique in 32 PWH before cART initiation and after 1, 6 and 12 months. To mimic bacterial and viral infections we used a panel of three stimuli (lipopolysaccharide (LPS), resiquimod (R848), and polyinosinic:polycytidylic acid (Poly I:C)) to stimulate the extracellular Toll-like receptor (TLR) 4 and the intracellular TLR7/8 and TLR3, respectively. The following cytokine responses were analyzed by Luminex 200: Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-12p40, IL17A, Interferon (IFN)-α, and IFN-γ.ResultsAt baseline PWH with nadir CD4+ T-cell count <350 cell/µL had lower levels of LPS-, R848-, and Poly I:C-induced IL-6 and IFN-γ, LPS- and R848-induced TNF-α and IL-12, LPS induced IL-1b, and R848-induced IL-10 than PWH with nadir CD4+ T-cell count >350 cells/µL. The majority (>50%) had induced cytokine concentrations below the reference intervals at baseline which was most pronounced for the LPS- and Poly I:C-induced responses. The induced responses in the whole population improved after 12 months of cART, and more PWH had induced cytokine concentrations within the reference intervals after 12 months. However, the majority of PWH still had LPS-induced INF-α, INF-γ and Poly I:C-induced TNF-α and IL-6 below the reference interval. The induced innate immune responses before cART initiation were not associated with the CD4+ T-cell recovery after 12 months of cART.ConclusionThe innate immune response was impaired in PWH, with a more pronounced impairment in PWH with low nadir CD4+ T-cell count. Initiation of cART improved the innate immune response, but compared to the reference intervals, some impairment remained in PWH without viral replication.

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“…A better understanding of the immunological mechanisms driving diverse COVID-19 disease trajectories is warranted to aid the management of patients with COVID-19 and identify new targets for interventions. In this prospective study, we applied a clinically implemented and standardized analysis assessing real-time whole-blood stimulated immune responses by TruCulture 34 , 46 , 47 in patients hospitalized with COVID-19. We identified early functional impairments in innate immune responses at the time of hospitalization associated with subsequent COVID-19 disease severity, and observed reconstitution of these impairments in recovering patients regardless of previous disease severity.…”

Section: Discussionmentioning

confidence: 99%

Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients

et al. 2022

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Background The immune pathogenesis underlying the diverse clinical course of COVID-19 is poorly understood. Currently, there is an unmet need in daily clinical practice for early biomarkers and improved risk stratification tools to help identify and monitor COVID-19 patients at risk of severe disease. Methods We performed longitudinal assessment of stimulated immune responses in 30 patients hospitalized with COVID-19. We used the TruCulture whole-blood ligand-stimulation assay applying standardized stimuli to activate distinct immune pathways, allowing quantification of cytokine responses. We further characterized immune cell subsets by flow cytometry and used this deep immunophenotyping data to map the course of clinical disease within and between patients. Results Here we demonstrate impairments in innate immune response pathways at time of COVID-19 hospitalization that are associated with the development of severe disease. We show that these impairments are transient in those discharged from hospital, as illustrated by functional and cellular immune reconstitution. Specifically, we identify lower levels of LPS-stimulated IL-1β, and R848-stimulated IL-12 and IL-17A, at hospital admission to be significantly associated with increasing COVID-19 disease severity during hospitalization. Furthermore, we propose a stimulated immune response signature for predicting risk of developing severe or critical COVID-19 disease at time of hospitalization, to validate in larger cohorts. Conclusions We identify early impairments in innate immune responses that are associated with subsequent COVID-19 disease severity. Our findings provide basis for early identification of patients at risk of severe disease which may have significant implications for the early management of patients hospitalized with COVID-19.

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Functional immune reconstitution early after allogeneic haematopoietic cell transplantation: A comparison of pre‐ and post‐transplantation cytokine responses in stimulated whole blood

Cited by 10 publications

References 45 publications

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

Improved induced innate immune response after cART initiation in people with HIV

Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients

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