Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma

Abstract

The limited benefits of immunotherapy against glioblastoma (GBM) is closely related to the paucity of T cells in brain tumor bed. Both systemic and local immunosuppression contribute to the deficiency of tumor-infiltrating T cells. However, the current studies focus heavily on the local immunosuppressive tumor microenvironment but not on the co-existence of systemic immunosuppression. Here, we develop a nanostructure named Nano-reshaper to co-encapsulate lymphopenia alleviating agent cannabidiol and lymphocyte recruiting cytokine LIGHT. The results show that Nano-reshaper increases the number of systemic T cells and improves local T-cell recruitment condition, thus greatly increasing T-cell infiltration. When combined with immune checkpoint inhibitor, this therapeutic modality achieves 83.3% long-term survivors without recurrence in GBM models in male mice. Collectively, this work unveils that simultaneous reprogramming of systemic and local immune function is critical for T-cell based immunotherapy and provides a clinically translatable option for combating brain tumors.

Nanotechnology Meets Stem Cell Therapy for Treating Glioblastomas: A Review

“…243 Chen's group explored doxorubicin-based nanodiamonds inducing autophagy in GBM cells, enhancing dendritic cell activation. 248 Persano et al induced ICD in U87 glioblastoma cells using iron oxide magnetic nanoparticles (IONC-GA-PEG) and mild hyperthermia, positively influencing NK cell recruitment and enhancing GBM susceptibility to NK cell-mediated killing. 250 Zhang et al synthesized bradykinin aggregation-inducedemission nanoparticles (BK@AIE NPs) with selective permeation of the BBB, demonstrating enhanced antitumor immunity through photothermal therapy-induced dead tumor cells (Figure 16).…”

“…Recent findings by Calabrese et al present evidence supporting the notion that GSCs are preserved within vascular niches resembling NSC environments . These results indicate the potential for selectively eliminating GSCs through a combination of antiangiogenic drugs, which can deplete the tumor blood supply and disrupt stem cell preservation, in conjunction with other chemotherapies and radiotherapies. , …”

“…ICD is achieved through various methods, including chemotherapy, radiotherapy, and hyperthermia . Chen’s group explored doxorubicin-based nanodiamonds inducing autophagy in GBM cells, enhancing dendritic cell activation . Persano et al induced ICD in U87 glioblastoma cells using iron oxide magnetic nanoparticles (IONC-GA-PEG) and mild hyperthermia, positively influencing NK cell recruitment and enhancing GBM susceptibility to NK cell-mediated killing .…”

Prodrug-loaded semiconducting polymer hydrogels for deep-tissue sono-immunotherapy of orthotopic glioblastoma

“…11 Nevertheless, the antitumor activity of current immunotherapies against GBM was far from satisfactory, which could be ascribed to the "cold" immunosuppressive tumor microenvironment (TME) of GBM and poor penetration of immunotherapeutic agents into tumors. [12][13][14][15][16][17] Glioma cells express increased amounts of immunosuppressive molecules, including programmed cell death 1 ligand (PD-L1) and indolamine 2,3-dioxygenase (IDO), which greatly attenuate the antigen-presenting effect. 18,19 Besides, the level of regulatory T cells (T reg ) is significantly increased in the GBM microenvironment, leading to the depletion of effector T cells.…”

Bifunctional Peptide Nanofibrils for Targeted Protein Degradation

“…Such property makes the Nano-PROTAC distinct from other recent nanoscale PROTAC advancements, including split-and-mix PROTAC (SM-PROTAC), [12] Gold nanocluster PROTAC (GNC-PROTAC), [13] carbon-dot (CD)-based PROTAC (CDTAC) [14] and DNA framework-based PROTAC (DbTAC). [15] The Nano-PROTACs were evaluated in vivo for their tumor-specific localization and retention using animal models. The injected Nano-PROTAC was able to quickly accumulate at tumor sites within 30 min and retain its localization for up to 72 h, and such tumor enrichment and retention was time-and dose-dependent.…”