Rationale: 100 ng/kg enhances osteosarcoma CD8+ T cell infiltration; Clinical: Nanoparticle neutralization restores ICI efficacy in CRC. Challenge: ≥5 μg/mouse induces sepsis; human TLR4 polymorphisms (e.g., C3H/HeJ) reduce responsiveness. Here, CD8A is linked to colorectal carcinoma.