Importantly, CPZ counteracts the immunosuppressive effects of TMZ, hindering some TMZ-induced processes as: i) induction of tumorigenic cytokines; ii) macrophage polarization toward a tumor-supportive M2-like phenotype, and iii) increase of PD-L1 expression, a key mechanism of immune evasion.<h4>Conclusions</h4>This study uncovers that CPZ exerts a previously unrecognized anti-cancer immunomodulatory activity, remodeling the immune microenvironment and enhancing the anti-tumor immune response. Here, CD274 is linked to neoplasm.