IL-6, NLR, and SII Markers and Their Relation with Alterations in CD8+ T-Lymphocyte Subpopulations in Patients Treated for Lung Adenocarcinoma.

Abstract

Simple SummaryLung cancer is the leading cause of cancer mortality worldwide. The most frequent group of lung cancer is the nonsmall cell lung carcinoma. The immune system of cancer patients participates in the crosstalk between inflammatory immune and nonimmune cells and cancer cells. This event is mediated by several molecules called cytokines. Lung cancer patients are frequently diagnostic at advanced stages, so chemotherapy is the major strategy for treatment. Various inflammatory factors have been described as prognostic biomarkers, such as the IL-6 cytokine, neutrophil–lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). In a cohort of patients with lung adenocarcinoma treated with conventional chemotherapy, changes in pro- and anti-inflammatory cytokines, mainly IL-6, the NLR, and SII, were studied. In addition, variations in the percentages of CD4+ and CD8+ T-lymphocyte subpopulations were investigated. Compared to healthy subjects, high levels of IL-6 were detected in patients prior to treatment. In the treated patient group with higher overall survival (OS), this cytokine decreased. Decreases in the NLR and SII values were detected from the third cycle of chemotherapy. Patients with lower OS had significantly lower CD8+ T-lymphocytes and its effector subpopulation. These parameters could be useful as predictive markers in lung adenocarcinoma.Cytokines, key contributors to tumorigenesis, are mediators between inflammatory immune or nonimmune and cancer cells. Here, IL-6 production by tumor cells was assessed in a cohort of patients with lung adenocarcinoma treated with conventional therapy. IL-6 levels and neutrophil–lymphocyte ratio (NLR) or systemic immune-inflammation index (SII) markers were evaluated. Changes in pro- and anti-inflammatory cytokines, HMGB1 concentration, and CD4+ and CD8+ T-lymphocyte populations and their subpopulations were investigated. IL-6 expression was detected immunohistochemically in lung adenocarcinoma biopsies. Cytokines were quantified using the cytometric bead array, and TGF-β and HMGB-1 through ELISA. Clinical parameters were collected to assess NLR and SII. CD4+ and CD8+ T-lymphocytes and naïve, memory, and effector subpopulations were quantified by flow cytometry. The data obtained were associated with patients’ median overall survival (OS). IL-6 showed the highest increase, probably because the lung adenocarcinoma cells produced IL-6. Patients with higher OS had lower NLR and SII from the third cycle of chemotherapy. Patients with lower OS had significantly lower percentages of CD8+ T-lymphocyte and its effector subpopulations, with a concomitant increase in the naïve subpopulation. This study suggests that in addition to the known inflammatory markers, IL-6, CD8+ T-lymphocytes and their effector and naïve subpopulations could be useful as predictive markers in lung adenocarcinoma.