Plasma IL-6 changes correlate to PD-1 inhibitor responses in NSCLC

Abstract

BackgroundBlood-based biomarkers of anti-solid tumor immune checkpoint blockade (ICB) response are lacking. We hypothesized that changes in systemic cytokine levels with the initial doses of programmed cell death protein 1 (PD-1) pathway inhibitors would correlate with clinical responses. New ultrasensitive ELISA technology enables quantitation of plasma proteins in sub-picogram-per-milliliter concentrations.MethodsWe measured plasma cytokines by ultrasensitive single-molecule array assays in patients with non-small-cell lung carcinoma before and during treatment with anti-PD-1 therapy. Association with best overall response and progression-free survival (PFS) was assessed by Kruskall-Wallis test and Kaplan-Meier plots with log-rank test, respectively.ResultsA decrease in interleukin 6 (IL-6) levels was associated with improved PFS (n=47 patients, median PFS: 11 vs 4 months, HR 0.45 (95% CI 0.23 to 0.89), p=0.04). The extent of change in IL-6 differed between best overall response categories (p=0.01) and correlated with changes in C reactive protein levels. We also explored plasma cytokine levels in relation to immune-related adverse effects and observed some correlation.ConclusionsThis study suggests the presence of a systemic, proteomic reflection of successful ICB outside the tumor microenvironment with plasma decreases in IL-6 and CRP.

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

“…Therefore, it might be an important approach not to interpret only the sole pre-therapeutic values, but also the dynamics of these markers. This gets support of some recent studies showing that increasing levels of NLR 23 , 24 , IL-6 5 and IL-8 15 under ICI treatment predict reduced response. On the other hand, increasing levels of INFγ have been found to improve response and survival in NSCLC patients treated with ICI 25 .…”

“…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 .…”

Discovery and validation of PZP as a novel serum biomarker for screening lung adenocarcinoma in type 2 diabetes mellitus patients

“…Although cytology is the gold standard for the diagnosis of malignancies, serum biomarkers are also invaluable in the screening and auxiliary diagnosis of malignant tumors as well as monitoring curative effects [ 24 , 25 ]. The serum proteome holds significant interest as a potential source of biomarkers and is an easily accessible fluid for auxiliary diagnosis.…”

Identification of Gene Markers for Survival Prediction of Lung Adenocarcinoma Patients Based on Integrated Multibody Data Analysis

“…Taking advantage of the molecular and cellular differences between tumor cells and normal cells, molecular targeted therapy targeting cell receptors, genes, and regulatory molecules as drug targets has gradually become a new strategy for the current clinical treatment of lung cancer, such as angiogenesis inhibitors and epidermal growth factor receptor inhibitors which have all been used in clinical applications. In addition, biological treatments including tumor vaccine technology, cytokine technology, monoclonal antibody technology, and gene therapy technology have gradually developed and transformed into clinical applications [16][17][18].…”