In the tumor microenvironment, high cholesterol levels can lead to CD8+ T cell exhaustion while inducing immune checkpoints, such as programmed cell death protein 1 (PD-1), natural killer cell receptor 2B4 (CD244), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and lymphocyte-activation gene 3 (LAG-3), via the ER stress sensor XBP1 signaling cascade [115]. The gene discussed is LAG3; the disease is neoplasm.