Human Vɣ9Vδ2 T cells spontaneously eliminate particular subsets of primary glioblastoma tumor cells
Cynthia Chauvin1.2, Ulrich Jarry1.2, Claire Pecqueur1.2 *, Emmanuel Scotet1.2 *
1 Inserm - UMR892, University of Nantes, CNRS - UMR 6299, Nantes, F-44000, France
2 LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, F-44000, France
* co-senior authors
Glioblastoma multiform (GBM) is the most frequent and aggressive primary brain tumor in adults, with a dismal prognosis and few therapeutic advances made over the last decade. Cellular immunotherapies are currently being explored to eliminate highly invasive and chemo/radioresistant GBM cells likely involved in rapid disease relapse. Non-alloreactive human Vɣ9Vδ2 T lymphocytes are able to kill a wide range of human tumor cells and display effector functions, setting them up as promising cell candidates for efficient immunotherapies.
We recently showed that immunodeficient NSG mice carrying orthotopic primary human GBM tumor xenografts recapitulate GBM tumor development in patients. Furthermore, we demonstrated that allogeneic human Vɣ9Vδ2 T cells can survive and patrol for several days within the brain parenchyma following adoptive transfer and successfully eliminate infiltrative primary GBM cells upon orthotopic aminobisphosphonate treatment. In order to bypass this sensitization process, several allogeneic human Vɣ9Vδ2 T cells have been isolated and amplified from PBMCs of healthy donors and screened for their ability to naturally and specifically react against human primary GBM cultures. Our results evidence that some Vɣ9Vδ2 T cell lines efficiently and preferentially eliminate particular subtypes of primary GBM tumor cells through cellular stress-associated molecular pathways that are currently under analysis and characterization.
Taken together, our results provide an important preclinical proof-of-concept for optimized targeted immunotherapies of brain tumors such as GBM and also identify key molecules and pathways that need to be defined before considering human ɣδ T cells in clinical approaches.