High systemic IL-6 is associated with worse prognosis in patients with non-small cell lung cancer

Abstract

Characteristic cytokine patterns have been described in different cancer patients and they are related to their diagnosis, prognosis, prediction of treatment responses and survival. A panel of cytokines was evaluated in the plasma of non-small cell lung cancer (NSCLC) patients and healthy controls to investigate their profile and relationship with clinical characteristics and overall survival. The case-controlled cross-sectional study design recruited 77 patients with confirmed diagnosis of NSCLC (cases) and 91 healthy subjects (controls) aimed to examine peripheral pro-inflammatory and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF and IFN-γ) by Cytometry Beads Arrays (CBA Flex) in. The cytokine IL-6 showed a statistically significant difference among groups with increased expression in the case group (p < 0.001). The correlation between the cytokines expression with patient’s clinical characteristics variables revealed the cytokine IL-6 was found to be associated with gender, showing higher levels in male (p = 0.036), whereas IL-17A levels were associated with TNM stage, being higher in III–IV stages (p = 0.044). We observed worse overall survival for individuals with high levels of IL-6 when compared to those with low levels of this cytokine in 6, 12 and 24 months. Further studies of IL-6 levels in independent cohort could clarify the real role of IL-6 as an independent marker of prognostic of NSCLC.

Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion

“…On the contrary, insulin-stimulated AKT/TBC1D4 signaling was 436 upregulated in skeletal muscle of tumor-bearing mice. This is surprising, given that tumor-bearing 437 mice displayed increased whole-body inflammation as indicated by increased spleen volume and 438 increased plasma levels of IL-6 and TNF-α, consistent with other investigations showing increased 439 IL-6 in patients with non-small cell lung cancers [49,50]. Inflammation would be expected to 440 reduce insulin signaling in muscle [51].…”

Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk

“…While other studies demonstrated the role of IL6 in promoting anti-tumor immunity through the stimulation of proliferation, survival and trafficking of T cells to lymph nodes and tumor sites, where T cells effectively shift tumor-suppressive state to responsive state to inhibit tumor growth and progression (89,90). An increased level of IL6 correlates with the poor prognosis and survival of lung cancer patients (54,60). TAM-derived IL6 plays a role in progression, invasion, angiogenesis, EMT, immune cell infiltration, and cancer stem cell (CSC) development and maintenance, through multiple unexplored molecular mechanisms (91)(92)(93).…”

Molecular cross‐talk of IL‐6 in tumors and new progress in combined therapy

“…The research and findings discussed indicate that IL‐6 overexpression is closely related to tumor activities, such as biogenesis, development, metastasis, and invasion. Related research has also indicated a significant negative correlation between the prognosis of NSCLC patients and IL‐6 concentrations in their serum . Therefore, inhibiting IL‐6 may be effective for impeding tumor development.…”

“…Related research has also indicated a significant negative correlation between the prognosis of NSCLC patients and IL-6 concentrations in their serum. 34 Therefore, inhibiting IL-6 may be effective for impeding tumor development.…”