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Re: survivor1x post# 736455

Monday, 12/09/2024 3:51:14 PM

Monday, December 09, 2024 3:51:14 PM

Post# of 819660
survivor, here is some additional detail from the original paper:

https://pmc.ncbi.nlm.nih.gov/articles/PMC3071163/

As shown in Figure 4, patients enrolled on our trial with the proneural gene expression signature had an overall survival that was indistinguishable from a set of 60 contemporary proneural tumors analyzed from UCLA and three other institutions (21) (p=0.664; Fig. 4A). In contrast to this, patients in our DC vaccine trial with mesenchymal gene expression signatures had a significantly extended survival compared with 82 concurrently collected tumors that were found to have these same gene expression signatures (p=0.0046; Fig. 4B). While these data are not intended to represent efficacy, such information is noteworthy because glioblastoma patients with mesenchymal gene expression patterns typically have the worst prognosis and are the most refractory to current therapies

Since the mesenchymal expression signature includes numerous genes associated with inflammation, and tumor-specific T cells are known to be attracted to pro-inflammatory signals, we evaluated whether patients on our DC trial with mesenchymal gene expression signatures also had increased tumor infiltrating lymphocytes (TILs). As shown in Figure 5, tumors with a mesenchymal gene expression signature had significantly increased CD3+ and CD8+ TILs compared with PN tumors (p=0.006)

If patients did not develop any toxic side effects from the experimental treatment and had stable disease for over three months, they received booster injections at the same dosage of tumor lysate-pulsed DC concurrently with either 5% imiquimod cream (Aldara™, a TLR-7 agonist) or poly-ICLC (Hiltonol™, a TLR-3 agonist). Due to initial safety/toxicity concerns of experimental allergic encephalomyelitis (EAE) (18) resulting from the combined use of DC vaccination and TLR agonists, these immune response modifiers were used only in the booster phase of the protocol, after patients had shown acceptable toxicity profiles to DC-lysate vaccinations alone.
Sorry - can't get the Figure pasted in use the link to see the figure
Figure 4.

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Extended survival in DC vaccinated patients with mesenchymal gene expression signatures, but not in patients with a proneural signature. The overall survival time of DC vaccine patients expressing a (A) Proneural (PN) gene signature (n=5) or (B) Mesenchymal (Mes) gene signature (n=9) was compared with the survival generated from a control, multi-institutional dataset of PN (n=60) or Mes glioblastomas (n=82; solid lines) previously published by our group (21). To accurately account for the potential bias associated with the time delay needed to generate the DC vaccine, we omitted control patients that experienced early progression (<250 days). PN comparison: p=0.664 (not statistically different, ns); Mes comparison (p=0.0046) by the Log-rank (Mantel-Cox) Test calculated in GraphPad software.
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