Dual MAPK Inhibition Triggers Pro-inflammatory Signals and Sensitizes BRAF Glioma to T Cell-Mediated Checkpoint Therapy.

BRAF pediatric low-grade gliomas frequently transform into high-grade gliomas (HGG) and poorly respond to chemotherapy, resulting in high mortality. Although combined BRAF and MEK inhibition (BRAFi+MEKi) outperforms chemotherapy, ∼70% of BRAF HGG patients are therapy resistant and undergo unbridled tumor progression. BRAF glioma have an immune-rich microenvironment suggesting that they could be responsive to immunotherapy but effects of BRAFi+MEKi on anti-tumor immunity are unclear.

Effect of organic biostimulants on cannabis productivity and soil microbial activity under outdoor conditions.

In 2019 and 2020, we investigated the individual and combined effects of two biofertilizers (manure tea and bioinoculant) and one humic acid (HA) product on cannabis biochemical and physiological parameters and soil CO evolution under outdoor conditions. Our hypothesis was that HA would increase the microbial activity in the biofertilizers and synergy of both compounds would promote better plant performance and stimulate soil microbial activity. In 2020, the individual and combined application of biofertilizers and HA increased cannabis height, chlorophyll content, photosynthetic efficiency, aboveground biomass, and bucked biomass by 105, 52, 43, 122, and 117%, respectively.

A paracrine circuit of IL-1β/IL-1R1 between myeloid and tumor cells drives genotype-dependent glioblastoma progression.

Monocytes and monocyte-derived macrophages (MDMs) from blood circulation infiltrate glioblastoma (GBM) and promote growth. Here, we show that PDGFB-driven GBM cells induce the expression of the potent proinflammatory cytokine IL-1β in MDM, which engages IL-1R1 in tumor cells, activates the NF-κB pathway, and subsequently leads to induction of monocyte chemoattractant proteins (MCPs). Thus, a feedforward paracrine circuit of IL-1β/IL-1R1 between tumors and MDM creates an interdependence driving PDGFB-driven GBM progression.

Monocyte depletion enhances neutrophil influx and proneural to mesenchymal transition in glioblastoma.

Myeloid cells comprise the majority of immune cells in tumors, contributing to tumor growth and therapeutic resistance. Incomplete understanding of myeloid cells response to tumor driver mutation and therapeutic intervention impedes effective therapeutic design. Here, by leveraging CRISPR/Cas9-based genome editing, we generate a mouse model that is deficient of all monocyte chemoattractant proteins.