DDIT3 and neoplasm: For instance, pharmacological inhibition of XBP1 or targeting other downstream sensors of ER stress, such as C/EBP homologous protein (CHOP) and protein kinase R-like endoplasmic reticulum kinase (PERK)/endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) have been shown to improve the effector function of tumor-reactive CD8+ T cells.3,4 The insightful work of Hwang et al. adds another exciting piece to the puzzle of overcoming the challenges of ER stress in TME.