Induction of T-helper-17-cell-mediated anti-tumour immunity by pathogen-mimicking polymer nanoparticles
Menée à l'aide de modèles murins, cette étude met en évidence l'intérêt d'administrer au niveau de la tumeur des nanocapsules constituées de mannanes et capables, en interagissant avec les cellules dendritiques, d'induire la différenciation des lymphocytes T CD4+ en lymphocytes Th7 pour favoriser le recrutement et l'activation des cellules immunitaires effectrices
The effectivity of cancer immunotherapies is hindered by immunosuppressive tumour microenvironments that are poorly infiltrated by effector T cells and natural killer cells. In infection and autoimmune disease, the recruitment and activation of effector immune cells is coordinated by pro-inflammatory T helper 17 (TH17) cells. Here we show that pathogen-mimicking hollow nanoparticles displaying mannan (a polysaccharide that activates TH17 cells in microbial cell walls) limit the fraction of regulatory T cells and induce TH17-cell-mediated anti-tumour responses. The nanoparticles activate the pattern-recognition receptor Dectin-2 and Toll-like receptor 4 in dendritic cells, and promote the differentiation of CD4+ T cells into the TH17 phenotype. In mice, intra-tumoural administration of the nanoparticles decreased the fraction of regulatory T cells in the tumour while markedly increasing the fractions of TH17 cells (and the levels of TH17-cell-associated cytokines), CD8+ T cells, natural killer cells and M1-like macrophages. The anti-tumoural activity of the effector cells was amplified by an agonistic antibody against the co-stimulatory receptor OX40 in multiple mouse models. Nanomaterials that induce TH17-cell-mediated immune responses may have therapeutic potential.