PTGS2 and neoplasm: Even if further and more wide-ranging studies are needed to deepen the effects of the COX-2 inhibitor on the TMZ ability to affect the TME in the context of GBM, our data emphasize the paradoxical and alarming pro-tumor effect of TMZ, a treatment that while inducing the recruitment of macrophages, promoted their M2-phenotypic shift, counteracting its efficacy and enriched tumor population with GSCs, resulting in a drug resistance increase.