Monday, September 1, 2014

Important aspect of immunomodulation, the case of the T-reg!

T cell Regulator have plenty of expression of FOXP3 (Scurfin) and this statement summarize the power of Foxp3,
Roli Khattri et al "express glucocorticoid-induced tumor-necrosis factor receptor–related (GITR) protein. The forced expression of Foxp3 also delays disease in CTLA-4-/- mice, indicating that the Scurfin and CTLA-4 pathways may intersect and providing further insight into the TR cell lineage."

Use of Azacytidine and other Histone modulating agents seems to increase Treg cells and therefore TNF receptor stimulation yielding an uncontrolled inflammatory effect leading to some level of Apoptosis.   The involvement of CTLA-4 must be clearly noticed!

What triggers the expansion of Foxp3 expressing cell is being debated :" the influence of solely TGF-β, so the difference between a proinflammatory and a pro-regulatory scenario is the presence of a single interleukin. IL-6 or IL-21 is being debated by immunology laboratories as the definitive signaling molecule. It seems so far that murine studies point to IL-6 whereas human studies have shown IL-21."  Wikipedia
could Vidaza induced expansion of Treg be compared with IL-21 induced Treg expansion for further answers?   Remembering that MGUS is TNF driven, is there a role here?

Could association of IL-23 expands the force of Ipilimumab?  or can Vidaza do it since there is a clear proclaimed link?

wait a minute, it gets better" Two lines of functional evidence strongly supported that FoxP3 serves as tumour suppressive transcription factor in cancer development. First, FoxP3 represses expression of HER2, Skp2, SATB1 and MYC oncogenes and induces expression of tumour suppressor genes P21 and LATS2 in breast and prostate cancer cells. Second, over-expression of FoxP3 in melanoma,[12] glioma, breast, prostate and ovarian cancer cell lines induces profound growth inhibitory effects in vitro and in vivo. However, this hypothesis need to be further investigated in future studies." Wikipedia

Is that means
1.In Her-2 negative disease, Vidaza may have a supportive role?
2.what in hell Skp2 add to this
3.MYC is proliferation in chief
4.LATS2 ?????
5. and of course P21, who saw this coming!

Then come this from Marsha Willis-Karp et al:"Tim-3, a member of the T cell immunoglobulin mucin family, is expressed by TH1 cells. Analysis of Tim-3–Tim3 ligand signaling now shows this pathway is intimately involved in the counter-regulation of T helper type 1 immune responses."

DOES THIS MEANS TIM-3 ENTERS THE PATHOGENESIS OF MUCINOUS CARCINOMA?  THESE TUMOR ARE NOTICED LATE AND GENERALLY MORE ADVANCED AT TIME OF DIAGNOSIS.
FUN LOOKING IN ALL THIS!

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