sHLA-G as a biomarker for colorectal cancer pathogenesis

Objectives: Colorectal cancer (CRC) is a serious gastrointestinal disease. Cancer cells can survive in a microenvironment that includes distinct immune cells, various immune checkpoints including HLA-G, and different immune effectors such as interleukin-6 (IL-6), TNF-alpha (TNF-α), and interferon-gamma (IFN-γ). Thus, the objective of this study was to investigate HLA-G involvement in CRC as a prognostic factor in the Tunisian population, both in its soluble form (sHLA-G) and in its form linked to extracellular vesicles (HLA-GEV). Additionally, we examined its association to the secretion of cytokines. Methods: Fifty Tunisian patients, diagnosed with CRC, matched with ninety-eight healthy blood donors (HD) were enrolled in this study. Levels of sHLA-G, HLA-GEV, IL-6, TNF-α, and IFN-γ were dosed in plasma samples using specific ELISA. For the functional assay, we assessed sHLA-G effects on the production of cytokines by stimulated T lymphocytes. We measured the concentration of IL-6, TNF-α, and IFN-γ produced by activated T lymphocytes pre-stimulated by plasma sHLA-G and HLA-GEV. Results: Our case-control analysis showed high concentration of both sHLA-G (8.8 [0–63] ng/ml vs. 2.1 [0–63] ng/ml, p