ER-mitochondrion interactions, particularly MFN2-mediated processes, regulate calcium homeostasis and metabolic adaptation.341 Signaling pathways involving PERK-mediated eIF2α phosphorylation enhance autophagy and metabolic reprogramming, ultimately strengthening antitumor responses.342 The transcriptional coactivator PGC-1α has emerged as a potential therapeutic target, as its expression is capable of protecting CTLs from exhaustion.343 Sustained Akt signaling can downregulate PGC-1α, compromising T-cell mitochondrial capacity and impairing tumor-specific responses. Here, AKT1 is linked to neoplasm.