Biology subjects

Vaccaro, A.

Publications and source records attributed to Vaccaro, A..

3 recordsLinked to original sources

bioRxiv2024

Cellular and molecular events organizing the assembly of tertiary lymphoid structures in glioblastoma

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates associated with improved prognosis in numerous tumors. To date, their prognostic value in central nervous system cancers and the events underlying their formation remain unclear. Here, we find that TLS correlate with improved survival in glioblastoma patients. Furthermore, combining spatial transcriptomics of human tissues with longitudinal studies in murine glioma, we establish that the assembly of T cell-rich clusters is a prerequisite for the development of canonical TLS, and show that CD4 T cells play a central role in this process. Indeed, we provide evidence that IL7R+CCR7+ Th1 lymphocytes with lymphoid tissue-inducing potential are recruited to TLS nucleation sites, where they can initiate TLS assembly by expressing lymphotoxin {beta}. Our work defines TLS as a potential prognostic factor in glioblastoma and identifies cellular and molecular mechanisms of TLS formation. These findings have broader implications for the development of TLS-inducing therapies for cancer. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/601824v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@78be05org.highwire.dtl.DTLVardef@1037706org.highwire.dtl.DTLVardef@7b64e1org.highwire.dtl.DTLVardef@11bfd5c_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

Reliable Particle Sizing in Vaccine Formulations using Advanced Dynamic LightScattering

Understanding the impact of lipid nanoparticles size on immunogenicity represents an important step for enabling the rapid development of novel vaccines against known or emergent diseases. Dynamic light scattering, also known as quasi-elastic light scattering or photon correlation spectroscopy, has established itself as an optimal analytical method to determine particle size due to its in-situ approach and fast measurements. However, its application to many systems of industrial relevance has been limited due to artifacts arising from multiple scattering. Results interpretation becomes severely compromised depending on the concentration of the system and the size of the particles. In this context, strong sample dilution is often required, bringing additional uncertainties to the formulation development process. Here, we show how advanced dynamic light scattering technology can filter out multiple scattering from the signal and yield fully accurate sizing measurements, regardless of the sample concentration. We illustrate this in a comparative study with standard dynamic light scattering using polystyrene beads as model suspension as well as a concentrated commercial lipid nanoparticle adjuvant (AddaVax).

biophysics↗

bioRxiv2021

Agonistic CD40 antibody therapy induces tertiary lymphoid structures but impairs the response to immune checkpoint blockade in glioma

Gliomas are brain tumors characterized by immunosuppression. Immunostimulatory agonistic CD40 antibodies (CD40) are in clinical development for solid tumors but are yet to be evaluated for glioma. Here, systemic delivery of CD40 led to cytotoxic T cell dysfunction and impaired the response to immune checkpoint inhibitors in preclinical glioma models. This was associated with an accumulation of suppressive CD11b+ B cells. However, CD40 also induced tertiary lymphoid structures (TLS). In human glioma, TLS correlated with increased T cell infiltration indicating enhanced immune responses. Our work unveils the pleiotropic effects of CD40 therapy in glioma, which is of high clinical relevance.

cancer biology↗