Borneres, J. | bioRxiv Science

bioRxiv2025

Intra-tumoral delivery of FLT3L with CXCR3/CCR5 ligands promotes XCR1+ DC1 infiltration and activates anti-tumor immunity

Tumor infiltration by XCR1 conventional dendritic cells (cDC1) correlates strongly with favorable prognosis and improved responses to immunotherapy. Yet, tumor-driven immunosuppressive programs restrict efficient cDC1 recruitment, highlighting the need for strategies increasing cDC1 access to the tumor microenvironment. Here, we establish a proof-of-concept cell-based immunotherapy that enhances the infiltration of circulating cDC1 progenitors and supports their local expansion. Intratumoral engraftment of autologous mesenchymal stromal cells engineered to express membrane bound FLT3L promotes cDC1 recruitment when combined with poly(I:C). We identify poly(I:C)-induced CXCL9 and CCL5 as essential chemokines controlling intratumoral cDC1 infiltration. Stromal cell-mediated local delivery of FLT3L together with CXCL9 and CCL5 is sufficient to enhance cDC1 infiltration in mice or humanized mice settings. Finally, this approach activates antitumor immunity and partially overcomes resistance to immune checkpoint blockade. Collectively, our data support the therapeutic potential of expanding intratumoral cDC1s through local and sustained delivery of FLT3L, CXCL9, and CCL5.

immunology↗

bioRxiv2021

Anti-microbiota vaccines modulate the tick microbiome in a taxon-specific manner

Anti-tick microbiota vaccines have been shown to impact tick feeding but its specificity has not been demonstrated. In this study we aimed to investigate the impact of immune targeting of keystone microbiota bacteria on tick performance, and tick microbiota structure and function. Vaccination against Escherichia coli, the selected keystone taxon, increased tick engorgement weight and reduced bacterial diversity in Ixodes ricinus ticks compared to those that fed on mice immunized against Leuconostoc mesenteroides, a non-keystone taxon or mock-immunized group. The abundance of Escherichia-Shigella, but not Leuconostoc was significantly reduced in ticks fed on E. coli-immunized mice and this reduction was correlated with a significant increase in host antibodies (Abs) of the isotype IgM and IgG specific to E. coli proteins. This negative correlation was not observed between the abundance of Leuconostoc in ticks and anti-L. mesenteroides Abs in mice. We also demonstrated by co-occurrence network analysis, that immunization against the keystone bacterium restructure the hierarchy of the microbial community in ticks and that anti-tick microbiota vaccines reduced the resistance of networks to directed removal of taxa. Functional pathways analysis showed that immunization with a live bacterial vaccine can also induce taxon-specific changes in the abundance of pathways. Our results demonstrated that anti-tick microbiota vaccines can modulate the tick microbiome and that the modification is specific to the taxon chosen for host immunization. These results guide interventions for the control of tick infestations and pathogen infection/transmission.

immunology↗