Quinolinic acid (QA) is a product of tryptophan degradation and may serve as a precursor for nicotinamide adenine dinucleotide (NAD+), an important enzymatic cofactor for enzymes such as the DNA repair protein poly(adenosine diphsophate[ADP]-ribose)polymerase. Pathologic accumulation of QA has been found in neurodegenerative disorders including Alzheimer's and Huntington's disease, where it is thought to be toxic for neurons by activating the NMDA receptor and inducing excitotoxicity. While many tumors including gliomas constitutively catabolize tryptophan, it is unclear whether QA is produced in gliomas and whether it is involved in tumor progression. Here we show that QA accumulated in human gliomas and was associated with a malignant phenotype. QA was produced by microglial cells as expression of the QA-producing enzyme 3-hydroxyanthranilate oxygenase (HAAO) was confined to microglia in glioma tissue. Human malignant glioma cells but not non-neoplastic astrocytes expressed quinolinic acid phosphoribosyltransferase (QPRT) to utilize QA for NAD+ synthesis and prevent apoptosis when de novo NAD+ synthesis was blocked. Oxidative stress, temozolomide and irradiation induced QPRT in glioma cells. QPRT expression increased with malignancy. In recurrent glioblastomas after radiochemotherapy, QPRT expressionwas associated with a poor prognosis in two independent datasets. Our data indicate that neoplastic transformation in astrocytes is associated with a QPRT-mediated switch in NAD+ metabolism by exploiting microglia-derived QA as an alternative source of replenishing intracellular NAD+ pools. The elevated levels of QPRT expression increases resistance to oxidative stress induced by radiochemotherapy, conferring a poorer prognosis. These findings have implications for therapeutic approaches inducing intracellular NAD+ depletion such as alkylating agents or direct NAD+ synthesis inhibitors and identify QPRT as a potential therapeutic target in malignant gliomas.