Fig. 4: Activation mechanism of innate immunity.
From: A vaccine-based nanosystem for initiating innate immunity and improving tumor immunotherapy
a Identification of differentially expressed genes in 4T1 tumors 3 days after intratumoral injection with siRNA2@HPVP or aPDL1. Differential genes in the GO term of the immune process were labeled. Three biological replicates are shown. b GeneMANIA for predicting gene interactions between differential genes in the GO term of the immune process. c KEGG enrichment analysis of the pathways involved in the biological effect induced by siRNA2@HPVP treatment. d PCR analysis of the transcript abundance of Tlr7, Cxcl9, Infb1, Ifngr1, and Ifng genes in 4T1 tumors after different treatments. Three biological replicates are shown. e Schematic diagram of the possible mechanism for siRNA2@HPVP to activate the innate immunity. siRNA2@HPVP activates APCs via the TLR7-mediate pathway, and then recruits TH1 cells for anticancer effect via their inherent immunogenicity and IFNs pathway. f HEK-293 cells transiently expressing TLR homodimers and ELAM-Luc reporter plasmid proved that the immune response mediated by siRNA2@HPVP is TLR7-dependent. Three biological replicates are shown. g Blockade of type I IFN pathway with anti-IFNAR1 antibody (aifnar, 200 μg per mice, i.p.) suppressed the therapeutic effect of siRNA2@HPVP (7.5 mg kg−1) treatment. Tumor size was recorded every other day (left, four biological replicates are shown). The proportion of tumor-infiltrating CD8+ T lymphocytes reduced when the IFN pathway was blocked (right, four biological replicates are shown). h Quantitative analysis of T-bet (left) and CD4 (right) expressions in 4T1 tumors through the immunofluorescence staining after different treatments. Tumor tissues were obtained 15 days after different treatments. Six images per group were taken. Statistical significance was calculated with two-tailed Student’s t test (a) one-way ANOVA with Tukey post-hoc analysis (d, f, g, h). Data are presented as mean values ± SD.
