| Autor: |
Claire Pecqueur, Emmanuel Scotet, Henri Vié, François M. Vallette, Xavier Saulquin, Laetitia Gautreau-Rolland, Catherine Gratas, Lisa Oliver, Christelle Retière, Catherine Willem, Laura Lafrance, Ulrich Jarry, Jeanne Perroteau, Noémie Joalland, Cynthia Chauvin |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6527729.v1 |
| Popis: |
Purpose:Cellular immunotherapies are currently being explored to eliminate highly invasive and chemoradioresistant glioblastoma (GBM) cells involved in rapid relapse. We recently showed that concomitant stereotactic injections of nonalloreactive allogeneic Vγ9Vδ2 T lymphocytes eradicate zoledronate-primed human GBM cells. In the present study, we investigated the spontaneous reactivity of allogeneic human Vγ9Vδ2 T lymphocytes toward primary human GBM cells, in vitro and in vivo, in the absence of any prior sensitization.Experimental Design:Through functional and transcriptomic analyses, we extensively characterized the immunoreactivity of human Vγ9Vδ2 T lymphocytes against various primary GBM cultures directly derived from patient tumors.Results:We evidenced that GBM cells displaying a mesenchymal signature are spontaneously eliminated by allogeneic human Vγ9Vδ2 T lymphocytes, a reactivity process being mediated by γδ T-cell receptor (TCR) and tightly regulated by cellular stress–associated NKG2D pathway. This led to the identification of highly reactive Vγ9Vδ2 T lymphocyte populations, independently of a specific TCR repertoire signature. Moreover, we finally provide evidence of immunotherapeutic efficacy in vivo, in the absence of any prior tumor cell sensitization.Conclusions:By identifying pathways implicated in the selective natural recognition of mesenchymal GBM cell subtypes, accounting for 30% of primary diagnosed and 60% of recurrent GBM, our results pave the way for novel targeted cellular immunotherapies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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