CD8A and neoplasm: The PD-1-PD-L1 axis remains a dominant pathway: IFN-γ produced by activated T cells induces PD-L1 expression on tumor cells (22), which in turn binds PD-1 on CD8+ T cells, delivering potent inhibitory signals that attenuate TCR signaling (e.g., reduced ZAP70 phosphorylation), cytokine secretion (e.g., IFN-γ), and cytotoxic activity, ultimately driving CD8+ T cells into a dysfunctional state.