Recent patient-linked and preclinical data identify hexa-acylated LPS (typical of Enterobacteriaceae) as a potent toll-like receptor 4 (TLR4) agonist that is required for full anti-PD-1 efficacy; oral hexa-acylated LPS boosts intratumoral CD8+ T-cell effector function and tumor control, whereas penta-acylated LPS (common in Bacteroidota) fails to enhance therapy and can antagonize hexa-LPS–induced activation [156]. Here, CD8A is linked to neoplasm.