Furthermore, recent findings by Zhang et al. on the PI3K/AKT/mTOR signaling pathway in macrophages, in the context of IL-4-induced metabolic shifts, add another layer of complexity.349,350 These shifts, including increased glycolysis and lactic acid production, alongside the upregulation of FcγRIIB expression, are thought to contribute to an immunosuppressive TME that disrupts CD8 + T cell function and accelerates tumor growth.350 Targeting FcγR interactions or modifying the Fc sequences of anti-PD-1 antibodies may present a promising strategy to mitigate HP and enhance the efficacy of ICIs. This evidence concerns the gene CD8A and neoplasm.