Tmic-19. targeting tumor-myeloid cell symbiosis in glioblastoma

Abstract Heterotypic interactions across diverse cell types of the tumor microenvironment can enable tumor progression and offer points for potential therapeutic intervention. Employing glioblastoma (GBM), a lethal form of brain tumor in adults, as a model system, we sought to (i) understand the nature of specific oncogenic signals in glioma cells that affects myeloid cell biology; (ii) identify myeloid cell factors which may support glioma growth and survival, (iii) develop novel therapeutic strategies targeting the tumor-myeloid cell symbiosis; and (iv) investigate whether blockade of this symbiosis can overcome the primary resistance of immunotherapy. Specifically, the novel oncogenic signals (e.g., CLOCK and TFPI2) and myeloid cell components of microglia and myeloid-derived suppressor cells will be discussed and highlighted. The findings from our studies demonstrate that the newly identified context-dependent tumor-myeloid cell symbiotic interactions not only promote tumor progression but also induce immune checkpoint inhibitor (ICI) therapy resistance in GBM. Thus, our studies provide novel therapeutic targets and offer a great potential to overcome immunotherapy resistance in GBM.