The TIGIT/CD155 axis plays a critical role in extracellular-mediated programming of the glioblastoma microenvironment

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B980
Abstract ID: 7914

Presenting Author:
Mohammad Asad , Postdoctoral Research Fellow at Albert Einstein Col. of Med.

Abstract:

Glioblastoma (GBM), the most common and deadly primary brain tumor, exerts profound local and systemic immunosuppressive effects through a variety of mechanisms. Tumor-derived extracellular vesicles (EVs) are increasingly appreciated as critical mediators of these effects. In surveying the tumor-immune microenvironment in samples of ultrasonic aspirate collected during surgical resection of GBM (n=10), we identified several key immunomodulatory markers expressed across a range of myeloid cell populations. Particularly, we found TIGIT, a classically understood as a T cell inhibitory protein, expressed across a range of myeloid cell populations in patient samples, including in myeloid-derived suppressor cells (MDSCs, 46.84±16.78% of total monocytic MDSCs). Using EVs collected from patient-derived cell lines, we were able to recapitulate these effects upon co-culture with monocytes derived from the peripheral blood of healthy donors (n=7). Furthermore, these induced MDSCs exhibit a profound T cell inhibitory effect (70.97±8.454%, compared to control 19.4±5.71; p<0.03), concomitant with a surge in Th2 immune responses via TIGIT/CD155 axis. In summary, our study identifies a novel EV-induced TIGIT upregulation in myeloid cells as a potentially crucial immunosuppressive mechanism in glioblastoma, and one with novel clinically translatable therapeutic applications both in terms of immune checkpoint blockade and inhibition of EV signaling.