Potential predictive value of change in inflammatory cytokines levels subsequent to initiation of immune checkpoint inhibitor in patients with advanced non-small cell lung cancer

Lim, Jeong Uk; Yoon, Hyoung Kyu

doi:10.1016/j.cyto.2020.155363

Cited by 29 publications

(28 citation statements)

References 62 publications

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“…In our study cohort, we found that patients with primary progression under ICI had significantly increased levels of IL-6 and IL-8, both markers of acute inflammation. This is consistent with other studies showing that both cytokines might be promising biomarkers in NSCLC immunotherapy 6 , 14 , 15 .…”

Section: Discussionsupporting

confidence: 93%

“…However, the value of inflammatory cytokines in the immune response derived from ICI treatment is poorly understood. First results indicate that markers of acute inflammation such as IL-6 or IL-8 are associated with reduced response 5 , 6 . Furthermore, markers of lymphocytic immune response as TNF-α, IFN-γ or IL-10 have be linked to better results under ICI treatment 6 .…”

Section: Introductionmentioning

confidence: 95%

“…First results indicate that markers of acute inflammation such as IL-6 or IL-8 are associated with reduced response 5 , 6 . Furthermore, markers of lymphocytic immune response as TNF-α, IFN-γ or IL-10 have be linked to better results under ICI treatment 6 . However, conclusive and especially prospective data on the impact of inflammation and cytokine profiles on the success of ICI therapy in NSCLC patients are missing.…”

Section: Introductionmentioning

confidence: 95%

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Systemic inflammation and pro-inflammatory cytokine profile predict response to checkpoint inhibitor treatment in NSCLC: a prospective study

Kauffmann-Guerrero

Kahnert

Kiefl³

et al. 2021

Sci Rep

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Treatment with single agent immune checkpoint inhibitors (ICIs) has tremendously changed second line therapy in NSCLC. However, there are still no reliable biomarkers predicting response and survival in this group of patients. PD-L1 revealed to be a correlating, but no perfect marker. Therefore, we sought to investigate in this prospective study, whether inflammation status and cytokine profile could serve as additional biomarkers guiding treatment decision for single agent ICIs in NSCLC. 29 stage IV NSCLC patients receiving single agent PD-1 checkpoint-inhibitor in second line were prospectively enrolled. Inflammatory scores and cytokine profiles (IL-6, IL-8, IL-10, IFN-γ and TNFα) have been obtained before treatment and at the time of the first staging. Cytokine profiles were correlated with response and survival. Patients with signs of pre-therapeutic inflammation (elevated, NLR, SII, IL-6, IL-8) showed significantly lower response to ICI treatment and reduced PFS. Contrary, elevated levels of IFN-γ revealed to characterize a subgroup of patients, who significantly benefits from ICI treatment. Furthermore, low systemic inflammation and high levels of IFN-γ characterized patients with long term-response to ICI treatment. Pre-therapeutic assessment of inflammation and cytokine profiles has the ability to predict response and survival in NSCLC patients treated with single agent ICIs.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Systemic inflammation and pro-inflammatory cytokine profile predict response to checkpoint inhibitor treatment in NSCLC: a prospective study

Kauffmann-Guerrero

Kahnert

Kiefl³

et al. 2021

Sci Rep

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“…One cohort study supported the viewpoint that IL-1β level in peripheral blood is correlated with PD-L1 expression in lung tumor tissues and poor prognosis of lung cancer. And the levels of IL-6 and TNF-α are associated with the level of IL-1β (26). Compared with the extent of lung functions decline or airway leukocytes number, we doubted whether the increase of airway proin ammatory cytokine levels is more consistent with PD-L1 upregulation.…”

Section: Discussionmentioning

confidence: 94%

Cigarette smoke or motor vehicle exhaust exposure induces PD-L1 upregulation in lung epithelial cells in COPD model rats.

Chen

Wang³

et al. 2021

Preprint

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Cigarette smoking and ambient air pollution are common risk factors for COPD and lung cancer. However, the underlying mechanism between COPD prevalence and lung cancer is remained elusive. In this study, we established rat COPD model through exposure to cigarette smoke (CS) or motor vehicle exhaust (MVE). The model rats developed COPD-like phenotypes, manifested as lung functions decline, lung inflammation and airway remodeling. The Programmed death-ligand 1 (PD-L1), a factor contributing to immune escape of tumor cells, was overexpressed in lungs from COPD model rats. The inflammatory responses and PD-L1 upregulations were also observed in cultured human bronchial epithelial cells BEAS-2B upon treatment with cigarette smoke extract (CSE) or diesel related particulate matter 2.5 (PM2.5, SEM1650b). Furthermore, both CS/CSE and MVE/PM2.5 induced ERK1/2 activation, a kinase mediating PD-L1 upregulation in premalignant bronchial cells or NSCLC cells, in COPD rats’ lungs or in BEAS-2B cells. Activations of STAT1/3, which was reportedly associated with PD-L1 expression in lung tumors, were detected in lungs from CS- or MVE-induced COPD model rats. However, CSE preferred to activate STAT3 and PM2.5 inclined to activate STAT1 in BEAS-2B cells. Therefore, we proposed that cigarette smoke and ambient air pollution elevate the risk of lung cancer in COPD patients by increasing PD-L1 expression in lung epithelial cells, suggesting the effects of immunesuppressive microenvironment on promoting tumorigenesis in COPD patient’s lung.

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“…Predictive values of inflammatory cytokines for the immunotherapy response have been studied in NSCLC (40), and one such study including two cohorts of SCLC patients evaluated the predictive value of cytokines in SCLC patients under immunotherapy. Changes in the levels of various cytokines, including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IFN-γ, were compared between the patients treated with chemotherapy only and those treated with chemotherapy plus ipilimumab.…”

Section: Autoantibodies and Cytokinesmentioning

confidence: 99%

A narrative review of current and potential prognostic biomarkers for immunotherapy in small-cell lung cancer

Lim¹,

Kang²

2021

Ann Transl Med

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Small-cell lung cancer (SCLC) is a highly invasive and rapidly proliferating pathologic subtype that accounts for 13-15% of all lung cancer cases. Recently in extensive-stage SCLC, treatments that combine immunotherapy and chemotherapy showed increased efficacy compared to chemotherapy alone in several trials. However, the combination of immunotherapy and conventional chemotherapy regimens was introduced only recently for extensive-stage SCLC, with relatively little real-world data. The demand for reliable biomarkers that can predict the efficacy of immunotherapy in SCLC is high. Several studies evaluated various parameters including programmed cell death ligand-1 (PD-L1) expression, tumor mutation burden (TMB), gene expression profiling, autoantibody, and blood cytokines for predictive value for response to immunotherapy in SCLC. Despite some observed correlations, there is a lack of concrete support for the use of PD-L1 expression levels for readily available biomarker. High TMB in combination with smoking history is predictive of a better response to immunotherapy, but validation of cutoffs and testing methods is necessary before it can be widely applied in clinical settings. Other candidate biomarkers such as immune cell distribution among tumor microenvironment, and systemic inflammatory markers can also be evaluated, after an accumulation of real-life data from SCLC patients under immunotherapy.

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Potential predictive value of change in inflammatory cytokines levels subsequent to initiation of immune checkpoint inhibitor in patients with advanced non-small cell lung cancer

Cited by 29 publications

References 62 publications

Systemic inflammation and pro-inflammatory cytokine profile predict response to checkpoint inhibitor treatment in NSCLC: a prospective study

Systemic inflammation and pro-inflammatory cytokine profile predict response to checkpoint inhibitor treatment in NSCLC: a prospective study

Cigarette smoke or motor vehicle exhaust exposure induces PD-L1 upregulation in lung epithelial cells in COPD model rats.

A narrative review of current and potential prognostic biomarkers for immunotherapy in small-cell lung cancer

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