A direct comparison of IFN-alpha and pegylated IFN-alpha did not reveal any significant differences in tumor growth inhibition indicating that this novel and more stable class of IFN is functionally equivalent.
Delivery of DNA vaccines encoding XBP1 and tumor Ag to skin DC resulted in increased IFN-α production by plasmacytoid DC (pDC) from skin/tumor draining lymph nodes and the cross-priming of Ag-specific CD8(+) T cell responses associated with therapeutic benefit.
MicroRNA-21 (miR-21) is overexpressed in many human tumors and has been linked to various cellular processes altered in cancer. miR-21 is also up-regulated by a number of inflammatory agents, including IFN, which is of particular interest considering the close relationship between inflammation and cancer.
Interestingly, the engagement of the receptor by TLR3 agonists can directly inhibit cell proliferation and induce tumor cell death when combined to treatment with either type I IFN or protein synthesis inhibitors.
Recent evidence has indicated that spontaneous activation of the Stimulator of Interferon Genes (STING) pathway within tumor-resident dendritic cells leads to type I IFN production and adaptive immune responses against tumors.
Animals vaccinated with gamma-IFN-secreting D122 cells produced by AAV-based plasmids delivery demonstrated a significant delay in footpad tumor growth when compared with controls and DIF2 cells.
The concentration of a Treg-inhibitory cytokine, interleukin (IL)-6, was correlated with the IFN-α expression level in tumors, and intratumoral CD11c(+) cells produced IL-6 in response to IFN-α stimulation.
We analyzed 19 samples of various astrocytic tumors (3 astrocytomas, 5 anaplastic astrocytomas, and 11 glioblastomas) for loss of heterozygosity (LOH) on chromosome 9p at 6 microsatellite loci (D9S54, IFNA, D9S171, D9S104, D9S165, and D9S166).
These results suggest active tobacco use in HNSCC has an immunosuppressive effect through inhibition of tumor infiltration of cytotoxic T-cells, likely as a result of suppression of IFN response pathways.
Using this probe, FISH analysis of primary glioblastoma tumors revealed homozygous deletions of the CDKN2 region in 6 of 9 tumors (67%) whereas a yeast artificial chromosome probe containing the interferon type I (IFN) gene cluster was deleted in only 4 cases (44%).
To search for genetic changes in SP, a microdissection-based genetic analysis using polymorphic markers at 9q22 (PTCH; D9S15, D9S303, D9S287, D9S252) as well as markers at 9p21 flanking the tumor suppressor gene p16 (IFNA, D9S171) was performed.
Current standard treatments for patients with metastatic (stage IV) renal cell carcinoma involve both surgical removal of tumors and treatment with biological agents such as interleukin 2 or IFN-α.
IL-27 augmented the expression of IFN regulatory factor (IRF)-1 and IRF-8, which possess tumor suppressor activities, in B16F10 transfectants expressing wild-type WSX-1.
Experimental data derived from mouse B16 malignant melanoma models indicates that the weight of tumor in mice treated with IFN fusion proteins was significantly smaller than that of mice treated with interferon-gamma alone.
Most importantly, PSar-IFN is significantly more potent in inhibiting tumor growth and elicits considerably less anti-IFN antibodies in mouse than PEG-IFN.
However, these data suggest that another tumor suppressor gene on 9p (near the IFNA locus) may contribute to the progression of differentiated adenocarcinoma of the stomach.
Emodin also sensitized the antiproliferative effect of IFN-α in HeLa cervical carcinoma cells and reduced tumor growth in Huh7 hepatocellular carcinoma-bearing mice.
Cervical biopsy samples from control women or those without neoplasia or HPV infection displayed higher IFN-alpha receptor expression than those with CIN, while simultaneous expression of both IFN-alpha receptor subunits was found only in the control group.
We demonstrate here that this effect, independent of cell contact, is not inducible in the presence of tumor lysates and requires the constitutive expression of IFN stimulated gene 15 (ISG15) by malignant cells.
Functionally, induction of ARG1 limited the therapeutic effect of IFN, as inhibition of arginase activity could strongly synergize with poly(I:C) to enhance CD8<sup>+</sup> T cell responses to thwart tumor growth in mice.
Our analysis demonstrates that tumors infiltrated by CD8<sup>+</sup> T cells expressing higher levels of activation marker (PD1<sup>hi</sup>) along with TCR signaling genes and cytolytic T cell markers (IL2<sup>hi</sup>/TNF-α<sup>hi</sup>/IFN-γ<sup>hi</sup>/GZMA-B<sup>hi</sup>) extend survival, whereas survival benefit was absent for tumors infiltrated by anergic and hyperexhausted CD8<sup>+</sup> T cells characterized by high expression of <i>CTLA-4, TIM3, LAG3</i>, and genes linked to PI3K signaling pathway.