The Kynurenine/Tryptophan Ratio and Glioblastoma Patients Treated with Hsppc-96 Vaccine.

The discovery that immunotherapy is a clinically-relevant approach for the treatment of malignant tumors is revolutionizing patient care. In adults diagnosed with glioblastoma (GBM), an aggressive and incurable primary brain tumor, autologous HSPPC-96 vaccination provides a significant increase in overall survival. However, all GBM patients eventually succumb to their disease, providing rationale for discovering new methods that proactively identify individuals that will respond, optimally. Of the immunosuppressive mediators that contribute to the inhibition of productive tumor immunity, indoleamine 2,3 dioxygenase 1 (IDO1), a rate-limiting enzyme that catabolizes tryptophan (Trp) into kynurenine (Kyn), has been demonstrated to be expressed at elevated levels in patients with malignant glioma. Recently, our group determined that a correlation exists between peripheral blood Trp and Kyn levels in GBM patients and the association with overall survival after HSPPC-96 treatment. Our findings indicate that the Kyn/Trp ratio may be a useful benchmark for identifying GBM patients with a higher likelihood to survive longer after vaccination. The relevance to future clinical trials, the limitations of brain tumor models to address these findings and the role of IDO1 versus tryptophan dioxygenase (TDO) in the maintenance of peripheral Trp and Kyn levels, is discussed.

Immunotherapy (Los Angeles, Calif.). 2016 Sep 09 [Epub]

Alicia Lenzen, Lijie Zhai, Kristen L Lauing, Galina Gritsina, Erik Ladomersky, Matthew Genet, C David James, Orin Bloch, Derek A Wainwright

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, USA; Department of Pediatrics, Northwestern University Feinberg School of Medicine, USA; Division of Hematology, Oncology and Stem Cell Transplantation, Northwestern University Feinberg School of Medicine, USA; Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, USA., Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, USA., Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, USA; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, USA; Brain Tumor Institute, Northwestern University Feinberg School of Medicine, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA., Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, USA; Department of Neurology, Northwestern University Feinberg School of Medicine, USA; Brain Tumor Institute, Northwestern University Feinberg School of Medicine, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA., Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, USA; Department of Medicine-Hematology/Oncology, Northwestern University Feinberg School of Medicine, USA; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, USA; Brain Tumor Institute, Northwestern University Feinberg School of Medicine, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.