MTX, a broad-spectrum anti-tumor anthracycline, has also been shown to induce ICD in melanoma, prostate cancer, osteosarcoma, and mouse colon cancer cells through an eIF2α phosphorylation-dependent mechanism, leading to anti-cancer immune responses (Bezu et al., 2018; Giglio et al., 2018; Qin et al., 2019; Li et al., 2020) (Figure 2). The gene discussed is EIF2A; the disease is cancer.