Impact of early inflammatory cytokine elevation after commencement of PD-1 inhibitors to predict efficacy in patients with non-small cell lung cancer

Ozawa, Yuichi; Amano, Yusuke; Kanata, Kei; Hasegwa, Hirotsugu; Matsui, Takashi; Kakutani, Takuya; Koyauchi, Takafumi; Tanahashi, Masayuki; Niwa, Hiroshi; Yokomura, Koshi; Suda, Takafumi

doi:10.1007/s12032-019-1255-3

Cited by 63 publications

(65 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cancer progression is associated with a pro-inflammatory environment (Lin and Karin, 2007;Lippitz, 2013). Dysregulation of cytokine interactions was involved in the pathogenesis of lung cancer (Zhang et al, 2016;Ozawa et al, 2019). High cytoplasmic RAP1 can increase cisplatin resistance of NSCLC combined with increased NF-κB activity (Xiao et al, 2017), and RAS-RAF-MEK-ERK signaling was a vital pathway that mediates ALK positive tumor cell survival in lung cancer (Hrustanovic and Bivona, 2016).…”

Section: Discussionmentioning

confidence: 99%

Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma

Zhang

Yang

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Lung squamous cell carcinoma (LSCC) is the most common subtype of non-small cell lung cancer. Immunotherapy has become an effective treatment in recent years, while patients showed different responses to the current treatment. It is vital to identify the potential immunogenomic signatures to predict patient' prognosis. The expression profiles of LSCC patients with the clinical information were downloaded from TCGA database. Differentially expressed immune-related genes (IRGs) were extracted using edgeR algorithm, and functional enrichment analysis showed that these IRGs were primarily enriched in inflammatory-and immune-related processes. "Cytokinecytokine receptor interaction" and "PI3K-AKT signaling pathway" were the most enriched KEGG pathways. 27 differentially expressed IRGs were significantly correlated with the overall survival (OS) of patients using univariate Cox regression analysis. A prognostic risk signature that comprises seven IRGs (GCCR, FGF8, CLEC4M, PTH, SLC10A2, NPPC, and FGF4) was developed with effective predictive performance by multivariable Cox stepwise regression analysis. Most importantly, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters, and also validated in two independent LSCC cohorts (GSE4573 and GSE17710). Potential molecular mechanisms and tumor immune landscape of these IRGs were investigated through computational biology. Analysis of tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinct immune landscape in high-and low-risk group. The study was the first time to construct IRG-based immune signature in the recognition of disease progression and prognosis of LSCC patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma

Zhang

Yang

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…Of note, elevated pretreatment levels of plasma IL-6, an immunosuppressive cytokine that may mediate anti-tumor immunity and response to anti-PD1/PD-L1 immunotherapy, were associated with worse outcomes. 36,37 While we cannot exclude that these changes are mainly due to the chemotherapy, it is important to note that the changes in VEGF, PlGF, VEGF-C, bFGF and sVEGFR1 are not consistent with those seen in the biomarker study conducted in the randomized ABC-03 study. 38 These data suggest that DKN-01 combined with gemcitabine/cisplatin significantly decreases these angiogenic biomarkers, and that evaluating their change is of value, as they appear to be related to the half-life and individual PK of DKN-01.…”

Section: Discussionmentioning

confidence: 83%

Phase I and Biomarker Study of the Wnt Pathway Modulator DKN-01 in Combination with Gemcitabine/Cisplatin in Advanced Biliary Tract Cancer

Goyal

Sirard²,

Schrag³

et al. 2020

Clinical Cancer Research

View full text Add to dashboard Cite

This study provides new insights on the effects of blocking Dickkopf-1 (DKK1), a modulator of Wnt signaling, using DKN-01. The phase I multicenter study tested the feasibility, efficacy and biological effects of DKN-01, a humanized monoclonal antibody targeting DKK1, in combination with gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers. The regimen was well tolerated but did not appear to have additional activity beyond historically reported efficacy with gemcitabine/cisplatin alone. Exploratory pharmacokinetic and biomarker data indicated potential antiangiogenic and immunomodulatory activity of DKN-01 and the need for increased dose intensity. Based on the above data and rationale, a phase II trial of DKN-01 combined with nivolumab has been initiated in patients with advanced refractory BTC (NCT04057365). Research.

show abstract

“…Phosphorylation of P65 and translocation of NF-κB dimers from the cytoplasm to the nucleus are favorable evidences for the activation of NF-κB. Meanwhile, the activation of NF-κB has long been linked to the production of inflammatory cytokines [31]. The expression of inflammatory factors plays an important role in the development of colon cancer [32].…”

Section: Discussionmentioning

confidence: 99%

AKR1B10 accelerates the production of pro-inflammatory cytokines via NF-κB signaling pathway in colon cancer

Liu¹,

Shi²,

Li³

et al. 2019

Preprint

View full text Add to dashboard Cite

Aldo-keto reductase family 1, member B10 (AKR1B10) has been reported to be involved in tumorigenesis of various cancer. In our studies, we evaluated the relationship between AKR1B10 expression and clinicopathological characteristics in colon cancer and showed that AKR1B10 expression was significantly correlated with TNM stage and clinical stage of colon cancer. It has been reported that colorectal cancer is closely associated with chronic inflammation and the underlying molecular mechanisms are still elusive. Here we found that knockdown of AKR1B10 significantly decreased the expression of the inflammatory cytokines, IL1α and IL6, induced by lipopolysaccharide (LPS) via inhibiting NF-κB signaling pathway. Furthermore, AKR1B10 depends on its reductase activity to affect the NF-κB signaling pathway and subsequently affect the production of inflammatory cytokines. In addition, knockdown of AKR1B10 effectively reduced cell proliferation and clonogenic growth, indicating the biologic role of AKR1B10 in colon cancer. Collectively, our findings provided important insights into a previously unrecognized role of AKR1B10 in colon cancer.

show abstract

Impact of early inflammatory cytokine elevation after commencement of PD-1 inhibitors to predict efficacy in patients with non-small cell lung cancer

Cited by 63 publications

References 31 publications

Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma

Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma

Phase I and Biomarker Study of the Wnt Pathway Modulator DKN-01 in Combination with Gemcitabine/Cisplatin in Advanced Biliary Tract Cancer

AKR1B10 accelerates the production of pro-inflammatory cytokines via NF-κB signaling pathway in colon cancer

Contact Info

Product

Resources

About