Could soluble levels of CD40L and galectin-9 be possible prognostic biomarkers and therapeutic targets in NSCLC?

Abstract

e21508 Background: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer. The immune system is now recognized to have the potential to destroy cancer cells. TIM-3 binds to Galectin-9 (GAL9) causing suppression of cytokine production, cell cycle arrest and cell death. Soluble CD40L (sCD40L) that is released by activated T lymphocytes and platelets. Therefore, we hypothesized that soluble forms immune checkpoint receptors and their ligands, such as TIM-3, GAL9 and CD40L may also prognostic implications of NSCLC. Objectives: Evaluate the soluble levels of CD40L, TIM-3 and GAL9 in patients with NSCLC in III and IV stages of disease. Methods: Samples of blood were collected from a cohort prospective involving 32 patients between 50 and 80 years old (65 + 8,6 years). Enzyme-linked immunosorbent assay was used to quantify expression these receptors. A non-parametric test was used to compare all groups (Mann-Whitney U-test). Statistical significance was defined as p<0.05. Data analysis was performed using GraphPadPrism v8.3. Results: Our results showed higher levels GAL-9 and TIM3 in patients with stage III and IV than controls ( p<0.05). As also, higher expression of CD40L was identified in patients stage III than stage IV ( p<0.0001) and controls ( p=0.007). It wasn’t seen significant different expression of CD40L between stage IV patients and controls. Analyzing GAL9, it was identified higher level in patients stage III than stage IV ( p<0.0001). Expression of TIM-3 wasn’t significant difference between patients with stage III and IV. When analysing in ratio between CD40L/TIM3, TIM3/GAL9 and CD40L/GAL9 in all groups, only TIM-3/GAL9 ratio had a positive correlation in patients stage IV (r=0.688; p<0.0001). By histology, patients with squamous cell carcinoma had higher levels of CD40L than adenocarcionoma ( p=0.01), but no significant difference was identified between expression of TIM3 e GAL9 and histological subtypes. Conclusions: This study showed expression sCD40L and GAL9 were higher stage III than stage IV in patients NSCLC. It can be inferred that soluble CD40L and GAL9 receptors are possible prognostic biomarkers and potential therapeutic targets in NSCLC.