Accordingly, the role of TLR agonists as cancer therapeutic agents is being revisited via the strategy of intra/peritumoral injection with the idea of stimulating the production of endogenous type I IFN inside the tumor.
Intravesical delivery of the gene encoding interferon results in an alternative strategy for IFN-based therapy of the disease, enabling sustained exposure of IFN protein that results from production by tumor and non-tumor cells in the urothelium.
These results indicate that the human IFN-con1 gene in a viral vector can be used successfully in the treatment of tumors both directly and by tumor-targeted gene therapy.
Thus, this study suggests that BID is crucial for cell viability regulated by IFN-α which can induce mitochondria-mediated apoptosis, indicating a notable potential to be a targeted therapy for IFN-α resistant tumors.
Consistent with STAT's limiting cell responsiveness to IFN, we found that 5-Aza-CdR treatment sensitized HT29 cells to growth inhibition by exogenous IFN-alpha2a, indicating that 5-Aza-CdR should be investigated as a potentiator of IFN responsiveness in certain IFN-resistant tumors.
Treatment of lymphoma-bearing mice with either IFN-DC vaccination or lenalidomide led to a significant decrease in tumor growth and lymphoma cell spread.
Microarray analysis showed high expression levels of IFN-stimulated genes in background liver samples and immune-related genes in tumor tissues of the IL-28B TG/GG genotype.
According to qRT-PCR data, expression levels of the endoplasmic reticulum-nuclei-1 (ERN1), Toll-like receptor 2 (TLR2), and human IFN regulatory factor 5 (IRF5) tumor suppressor genes elevated 2.05-, 2.08-, and 2.3-fold by ZA, respectively, in U87MG cells.
The IFN- secreted from CD8<sup>+</sup> T cells in the spleen also contributed to the better tumor inhibition profile in BIPI treatment group than in anti-PD-L1 or IL-2 treatment alone.
Here, we use human tumor explant cultures and cell culture models to show that the (ds) RNA Sendai Virus (SeV), poly-I:C, and rintatolimod (poly-I:C<sub>12</sub>U) all activate the TLR3 pathway involving TRAF3 and IRF3, and induce IFNα, ISG-60, and CXCL10 to promote CTL chemotaxis to <i>ex vivo</i>-treated tumors.
These data show that Ad.IFN-α2b has potential therapeutic benefit in MPM and that it generates anti-tumor immune responses that may induce anatomic and/or metabolic reductions in distant tumor.
Our results suggest that tumor vaccines with a potent immunoprotective effect do not necessarily have therapeutic potential and that weakly immunogenic tumors may be rendered highly immunogenic by cotransfection with the genes for B7.1 and gamma-IFN.
Our observations confirm that loss of DNA sequences on 9p, particularly the IFN genes, occurs at a significant frequency in gliomas, and may represent an important step in the progression of these tumors.
The local production of high concentrations of IL-2 and IFN-a at the tumor site may directly alter tumor properties associated with invasive and metastatic phenotypes of RCC.
Type I interferons (IFNα and IFNβ) directly regulate transcription of >100 downstream genes, which results in a myriad of direct (on cancer cells) and indirect (through immune effector cells and vasculature) effects on the tumour.
Elsewhere, we reported that multiple serial in vivo passage of a squamous cell carcinoma cells (SCC61) concurrent with ionizing radiation (IR) treatment resulted in the selection of radioresistant tumor (nu61) that overexpresses the signal transducer and activator of transcription 1 (Stat1)/IFN-dependent pathway.
The primary endpoint was the association between tumour hMLH1 or/and hMSH2-deficient and VEGF-1 expression; the relation between tumour MMR-status and IFL response rate was the secondary endpoint.
Targeted overexpression of hPNPase(old-35) might provide an effective therapeutic strategy for miR-221-overexpressing and IFN-resistant tumors, such as melanoma.
The level of IFN- or TNF- in the serum was detected and lymphocyte infiltration in the tumor tissue; the ratios of CD8+ T cells and CD4+ T cells in the spleen of mice were also analyzed.
Combination treatment and PEG-IFN monotherapy also significantly elevated the p53 protein and mRNA levels in the tumour but only combination treatment increased the degree of p53 phosphorylation at serine46 and induced p53-regulated apoptosis-inducing protein 1 (p53AIP1) expression.