Immune checkpoint inhibitors for the treatment of sepsis:insights from preclinical and clinical development

Rienzo, Mario; Skirecki, Tomasz; Monneret, Guillaume; Timsit, Jean François

doi:10.1080/13543784.2022.2102477

Cited by 12 publications

(5 citation statements)

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“…Engagement of PD-1 and TIM3 pathways on T lymphocytes leads to the inhibition of the second signal of T cell activation. High and sustained expression of the co-inhibitory molecules during persistent antigen stimulation has been shown to promote immune cells exhaustion in cancer, sepsis ( Rienzo et al, 2022 ) and chronic hepatitis B and C ( Osuch et al, 2020 ; Li et al, 2022 ). Several studies described a slight increase in PD-1 and/or TIM-3 lymphocyte expressions in acute alcoholic hepatitis/cirrhosis ( Markwick et al, 2015 ; Lebossé et al, 2019 ; Riva et al, 2021 ; Fadriquela et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Assessment of neutrophil subsets and immune checkpoint inhibitor expressions on T lymphocytes in liver transplantation: A preliminary study beyond the neutrophil-lymphocyte ratio

et al. 2023

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Background: Advanced stages of cirrhosis are characterized by the occurrence of progressive immune alterations known as CAID (Cirrhosis Associated Immune Dysfunction). In advanced cirrhosis, liver transplantation (LT) remains the only curative treatment. Sepsis, shares many similarities with decompensated cirrhosis in terms of immuno-inflammatory response. In both conditions, the neutrophil-lymphocyte ratio (NLR) is associated with poor outcomes. Based on alterations in sepsis, we hypothesized that we could observe in cirrhotic and LT patients more detailed neutrophil and lymphocyte phenotypes. To this end, along with leukocyte count, we assessed immature neutrophils, LOX-1+ MDSC and PD-1 and TIM-3 lymphocyte expressions in cirrhotic patients before transplantation in association with liver disease severity and during the first month after transplantation.Methods: We conducted a prospective monocentric study including cirrhotic patients registered on LT waiting-list. Blood samples were collected at enrolment before LT and for 1 month post-LT. In addition to NLR, we assessed by whole blood flow cytometry the absolute count of immature neutrophils and LOX-1+ MDSC as well as the expressions of immune checkpoint receptors PD-1 and TIM-3 on T lymphocytes.Results: We included 15 healthy volunteers (HV) and 28 patients. LT was performed for 13 patients. Pre-LT patients presented with a higher NLR compared to HV and NLR was associated with cirrhosis severity. Increased immature neutrophils and LOX-1+ MDSC counts were observed in the most severe patients. These alterations were mainly associated with acute decompensation of cirrhosis. PD-1 and TIM-3 expressions on T lymphocytes were not different between patients and HV. Post-LT immune alterations were dominated by a transitory but tremendous increase of NLR and immature neutrophils during the first days post-LT. Then, immune checkpoint receptors and LOX-1+ MDSC tended to be overexpressed by the second week after surgery.Conclusion: The present study showed that NLR, immature neutrophils and LOX-1+ MDSC counts along with T lymphocyte count and checkpoint inhibitor expression were altered in cirrhotic patients before and after LT. These data illustrate the potential interest of immune monitoring of cirrhotic patients in the context of LT in order to better define risk of sepsis. For this purpose, larger cohorts of patients are now necessary in order to move forward a more personalised care of LT patients.

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Section: Discussionmentioning

confidence: 99%

Assessment of neutrophil subsets and immune checkpoint inhibitor expressions on T lymphocytes in liver transplantation: A preliminary study beyond the neutrophil-lymphocyte ratio

et al. 2023

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“…Therefore, conducting studies to investigate the effect of ICI alone on immune cell subsets would be instructive. The recent interest in use of ICIs in earlier stage cancers and nonmalignant disease presents an opportunity to study the effect of ICI in conditions in which the tumor burden is either very low or absent ( 132 , 133 ). In addition, interrogating the lung microbiome could provide crucial data about potential disruptions that might contribute to CIP.…”

Section: Potential Targets For Future Researchmentioning

confidence: 99%

Pulmonary toxicity of immune checkpoint immunotherapy

Ghanbar,

Suresh

2024

Journal of Clinical Investigation

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Cancer remains a leading cause of mortality on a global scale. Lung cancer, specifically non–small cell lung cancer (NSCLC), is a prominent contributor to this burden. The management of NSCLC has advanced substantially in recent years, with immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), leading to improved patient outcomes. Although generally well tolerated, the administration of ICIs can result in unique side effects known as immune-related adverse events (irAEs). The occurrence of irAEs involving the lungs, specifically checkpoint inhibitor pneumonitis (CIP), can have a profound effect on both future therapy options and overall survival. Despite CIP being one of the more common serious irAEs, limited treatment options are currently available, in part due to a lack of understanding of the underlying mechanisms involved in its development. In this Review, we aim to provide an overview of the epidemiology and clinical characteristics of CIP, followed by an examination of the emerging literature on the pathobiology of this condition.

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“… 55 , 56 , 57 , 58 , 59 , 60 Therefore, novel immunotherapy is being evaluated for use in sepsis-induced immunosuppression through clinical trials. 61 , 62 , 63 A recent phase I RCT assessed the safety of anti-PD-L1 antibody in sepsis treatment. 64 The study enrolled 24 patients with sepsis-induced immunosuppression whose lymphocyte count was lower than 1.1 × 10 9 /L.…”

Section: Current Immunotherapy For Sepsis-induced Immunosuppressionmentioning

confidence: 99%

Clinical practice of sepsis-induced immunosuppression: Current immunotherapy and future options

Pei,

Gu,

Miao

et al. 2024

Chinese Journal of Traumatology

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Immune checkpoint inhibitors for the treatment of sepsis:insights from preclinical and clinical development

Cited by 12 publications

References 91 publications

Assessment of neutrophil subsets and immune checkpoint inhibitor expressions on T lymphocytes in liver transplantation: A preliminary study beyond the neutrophil-lymphocyte ratio

Assessment of neutrophil subsets and immune checkpoint inhibitor expressions on T lymphocytes in liver transplantation: A preliminary study beyond the neutrophil-lymphocyte ratio

Pulmonary toxicity of immune checkpoint immunotherapy

Clinical practice of sepsis-induced immunosuppression: Current immunotherapy and future options

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