Notably, various stressors in the TME can stimulate ERS not only in cancer cells but also in immune cells; for example, high levels of cholesterol in the TME can activate IRE1α–XBP1 signaling in T cells within cancer tissues, induce programmed death protein 1 (PD-1) expression, and prevent T cells from exerting tumor-killing effect (Ma and Yi, 2019). This evidence concerns the gene ERN1 and neoplasm.