Temozolomide alters the expression pattern of immune mediators in monocyte-derived dendritic cells

Monocyte-derived dendritic cells (moDCs) are widely used in cancer immunotherapy due to their accessibility and their ability to initiate potent T cell responses. However, the immunosuppressive tumor microenvironment often compromises the therapeutic efficacy of these treatments. Temozolomide (TMZ), an alkylating chemotherapeutic agent widely used in the treatment of glioblastoma, has been proposed to exert additional immunomodulatory effects beyond its cytotoxic role. This study was designed to evaluate the influence of TMZ on the phenotype and functional characteristics of human moDCs. Flow cytometry analysis revealed that TMZ treatment increased HLA-DR expression, whereas CD11c and CD86 expression did not change significantly. Gene expression analysis revealed a notable increase in interleukin (IL)-12 and tumor necrosis factor-alpha (TNF-α) transcripts, consistent with an enhanced immunostimulatory potential. TMZ also downregulates indoleamine 2,3-dioxygenase (IDO) and transforming growth factor-beta (TGF-β), both of which are associated with immunoregulatory pathways. The observed profile suggests that TMZ alone can modulate DC-associated immune mediators in a manner consistent with enhanced immunostimulatory features under controlled in vitro conditions. However, the translational relevance of these findings remains limited due to the absence of functional DC-T cell/natural killer (NK) cell assays and the lack of clinically relevant co-exposures, such as dexamethasone. While TMZ appears compatible with DC-based vaccine strategies, further functional studies are needed to clarify its net effect on T cell responses and to optimize its integration into combined immunotherapy regimens.