IL-6 Signaling Blockade during CD40-Mediated Immune Activation Favors Antitumor Factors by Reducing TGF-β, Collagen Type I, and PD-L1/PD-1

Eriksson, Emma; Milenova, Ioanna; Wenthe, Jessica; Moreno, Rafael; Alemany, Ramón; Loskog, Angelica

doi:10.4049/jimmunol.1800717

Cited by 36 publications

(28 citation statements)

References 48 publications

(64 reference statements)

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“…This indicated that high levels of IL-6 and IL-10 in non-survivors could provide an insight for adenovirus-associated nosocomial infection. IL-6 plays a role in immunosuppression by driving differentiation of myeloid suppressor cells together with TGF-β in cancer pathogenesis [29] .…”

Section: Discussionmentioning

confidence: 99%

A case series of children with adenovirus pneumonia: three-year experiences in a tertiary PICU

Shi

Zhong

Wang

et al. 2020

Preprint

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Background: Describe the outcome of adenovirus pneumonia in a pediatric intensive care unit (PICU) over a 3-year period, to identify the risk factors that may be associated with worse outcome.Methods: A retrospective observational study was performed in the PICU of children’s hospital in Shanghai from July 2016 to June 2019. Sixty-seven children over 29 days to 14 years old with adenovirus pneumonia who were admitted to PICU with acute hypoxemic respiratory failure were included in this study. The primary outcome was hospital mortality, and secondary outcomes were hospital and PICU length of stay (LOS), and risk factors of worse outcome.Results: Of 67 children with severe adenovirus pneumonia, the hospital mortality was 16.42 % (11/67) and 28-day mortality was 14.93 % (10/67). Median Pediatric Risk of Mortality III (PRISM III) score at admission was 13 (interquartile range[IQR], 10-15). Median PICU LOS stay was 11days (8-18d) and hospital LOS was 22 days (16-31d). Among children with extracorporeal membrane oxygenation (n=9), 6 cases survived and 3 cases died. The patients who need renal replacement therapy, neuromuscular blockade, parenteral nutrition, and packed red blood cell perfusion had higher hospital mortality ( p = 0.000, p = 0.041, p = 0.000, p = 0.012, respectively). Multivariate logistic analysis indicated that liver dysfunction and nosocomial infection were associated with high risk of mortality.Conclusions: The hospital mortality of adenovirus pneumonia in our PICU was 16.42%. Patients complicated liver dysfunction and co-infection & nosocomial infection were associated with poor outcome.

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Section: Discussionmentioning

confidence: 99%

A case series of children with adenovirus pneumonia: three-year experiences in a tertiary PICU

Shi

Zhong

Wang

et al. 2020

Preprint

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“…Hence, levels of serum IL-6 could be used to estimate the inflammatory status of the lung. However, immunotherapy could also increase the level of IL-6, especially in good responders, which may disturb its predictive effects [80].…”

Section: Immunologic Factorsmentioning

confidence: 99%

Radiation recall pneumonitis induced by PD-1/PD-L1 blockades: mechanisms and therapeutic implications

Teng

2020

BMC Med

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Background The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. Thus far, the underlying mechanism of this toxicity remains largely unknown. Main text In this review, we discuss the unique pattern of radiation recall pneumonitis (RRP) induced by PD-1 blockade. The clinical presentation is different from common radiation pneumonitis (RP) or RRP induced by cytotoxic drugs. The immune checkpoint inhibitors may evoke an inflammatory reaction in patients’ previously irradiated fields, with infiltrating lymphocytes and potential involvement of related cytokines. All RRP patients have showed durable response to anti-PD-1/PD-L1. RRP is manageable; however, interruption of checkpoint blockades is necessary and immunosuppressive treatment should be started immediately. Further analyses of the predictive factors, including RT dosimetric parameters, tumor-infiltrating lymphocytes (TILs), and PD-L1 expression, are needed given the wide use of immune checkpoint inhibitors and high mortality from lung toxicity with the combination treatment. Conclusion Immune checkpoint inhibitors may evoke an RRP in the patients’ previously irradiated fields. Interactions between immune checkpoint inhibitors and radiotherapy should be studied further.

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“…There are limited antiviral drugs available for adenovirus. Cidofovir is an antiviral drug which use has been associated with significant reductions of adenovirus load and, in some series improved survival in reports [10,23] . Until recently, Cidofovir is not available in China till 2019, and has been neither widely used in children, nor has it been used in our cases.…”

Section: Management and Outcomesmentioning

confidence: 99%

A case series of children with adenovirus pneumonia: three-year experiences in a tertiary PICU

Shi

Zhong

Wang

et al. 2020

Preprint

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Objective: Describe the outcome of adenovirus pneumonia in a pediatric intensive care unit (PICU) over a 3-year period, to identify the risk factors that may be associated with worse outcome. Design: A retrospective observational study was performed in a tertiary university PICU from July 2016 to June 2019. Setting: The PICU of children’s hospital in Shanghai. Patients: Sixty-seven children over 29 days to 14 years old with adenovirus pneumonia who were admitted to PICU with acute hypoxemic respiratory failure were included in this study. Measurements and Main Results: The primary outcome was hospital mortality, and secondary outcomes were hospital and PICU length of stay (LOS), and risk factors of worse outcome. Of 67 children with severe adenovirus pneumonia, the hospital mortality was 16.42 % (11/67) and 28-day mortality was 14.93 % (10/67). Median Pediatric Risk of Mortality III (PRISM III) score at admission was 13 (interquartile range[IQR], 10-15). Median PICU LOS stay was 11days (8-18d) and hospital LOS was 22 days (16-31d). Among children with extracorporeal membrane oxygenation (n=9), 6 cases survived and 3 cases died. The patients who need renal replacement therapy, neuromuscular blockade, parenteral nutrition, and packed red blood cell perfusion had higher hospital mortality ( p = 0.000, p = 0.041, p = 0.000, p = 0.012, respectively). Multivariate logistic analysis indicated that liver dysfunction and co-infection & nosocomial infection were associated with high risk of mortality. Conclusions: The hospital mortality of adenovirus pneumonia in our PICU was 16.42%. Patients complicated liver dysfunction and co-infection & nosocomial infection were associated with poor outcome.

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IL-6 Signaling Blockade during CD40-Mediated Immune Activation Favors Antitumor Factors by Reducing TGF-β, Collagen Type I, and PD-L1/PD-1

Cited by 36 publications

References 48 publications

A case series of children with adenovirus pneumonia: three-year experiences in a tertiary PICU

A case series of children with adenovirus pneumonia: three-year experiences in a tertiary PICU

Radiation recall pneumonitis induced by PD-1/PD-L1 blockades: mechanisms and therapeutic implications

A case series of children with adenovirus pneumonia: three-year experiences in a tertiary PICU

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