Infection by measles virus (MV) induces type I IFN via the retinoic acid-inducible gene I/melanoma differentiation-associated gene 5/mitochondrial antiviral signaling protein (MAVS) pathway in human cells.
In the molecularly defined low-risk subgroup, patients treated with high-dose IFN had a significantly improved RFS compared with patients in the other two subgroups (<i>P</i> < 0.05).<b>Conclusions:</b> These results validate the independent impact of combined expression levels of SPP1, RGS1, and NCOA3 on survival of melanoma in a prospectively collected cohort.<i></i>.
In a previous study on melanoma cell lines we found that greatest sensitivity to IFN was found in cell lines with the greatest number of copies of chromosome 9p, where the IFN gene family is located.
These data confirm the existence of a melanoma susceptibility gene on 9p and indicate that this locus most probably lies outside of the IFNA-D9S126 interval.
These results show that there is a specific disruption of IFN-alpha gene activation rather than IFN-beta in melanoma lines and suggest that this is due to disruption of a trans-acting IFN-alpha gene transcription factor.
Poly I:C was not able to induce melanocytes or melanoma cells to produce detectable amounts of IFN-alpha protein, but able to induce a significant amount of IFN-beta in melanocytes and two of the melanoma cell lines: MMAc and VMRC-MELG.
We hypothesized that restoration of IFN-stimulated genes by co-administration of the demethylating drug 5-aza-2'-deoxycitidine (decitabine [DAC]) may enhance the susceptibility to IFN-I-mediated antitumoral effects in melanoma.
Seventeen SN tested for loss of heterozygosity (LOH) at 9p and 10q regions, known to be frequently deleted in melanoma, showed LOH at the 9p loci D9S942 and IFNA.
In these contexts, targeted overexpression of hPNPase(old-35) might be a novel therapeutic strategy for c-myc-overexpressing and IFN-resistant tumors, such as melanomas.
To further determine the significance of this observation, 17 melanoma cell lines sensitive or resistant to the antiproliferative effects of IFN-alpha2 and IFN-beta, as well as 30 melanoma patient samples, were analyzed for Stat1 levels by either Western blot analysis or immunohistochemistry.
We conclude that a defect in the level of STAT1 and possibly all three ISGF3 components in IFN-resistant human melanoma cells may be a general phenomenon responsible for reduced cellular responsiveness of melanomas to IFNs.
The unique de novo and IFN-modified antigenic phenotype of cultures derived from different patients indicates that the antigenic phenotype displayed by melanoma cultures grown in vitro is genetically determined.
Patients who undergo surgical excision of stage III MM appear to enjoy prolonged DFS and OS when treated with TIL + IFN-<i>α</i> compared to IFN-<i>α</i> alone.
The antiproliferative, pro-apoptotic and immunomodulatory activity of BRAF-I and IFNα combination was tested in vitro and in vivo utilizing three melanoma cell lines, HLA class I-MA peptide complex-specific T-cells and immunodeficient mice (5 per group for survival and 10 per group for tumor growth inhibition).All statistical tests were two-sided.
In the PanScan data, initial associations were found with melanoma susceptibility variants in NCOA6 [rs4911442; OR, 1.32; 95% confidence interval (CI), 1.03-1.70; P = 0.03], YWHAZP5 (rs17119461; OR, 2.62; 95% CI, 1.08-6.35; P = 0.03), and YWHAZP5 (rs17119490; OR, 2.62; 95% CI, 1.08-6.34; P = 0.03), TYRP1 (P = 0.04), and IFNA13 (P = 0.04).
Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b.
Subtraction hybridization combined with induction of cancer cell terminal differentiation in human melanoma cells identified melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) and SARI (suppressor of AP-1, induced by IFN) that display potent antitumor activity.