T11TS Facilitate Effective Regeneration of Hematolymphopoiesis by Reversing the Gliomagenic Suppression of Lineage Restricted Progenitor Markers through Constitutive Regulation of Wnt and Notch Signaling
Somnath Mondal, PhD Fellow, Calcutta School of Tropical Medicine
Reversion of glioma-mediated global immunosuppression and constitutive regeneration of immune system could be one of the prime prognostic defensive keys against fatal malignant glioma. Coordinated activation of canonical Wnt and Notch signaling plays a pivotal role within the adult hematopoietic system particularly in modulating the process of hematolymphopoiesis. Gliomagenic regulation of either Wnt or Notch signaling mediators or lineage commitment progenitor markers within bone marrow milieu has not been elucidated. Our prior studies showed that the novel immunotherapeutic molecule T11-target structure (T11TS) repress gliomagenic apoptosis of bone marrow hematopoietic stem cells. We also demonstrated rejuvenation of BMHSC from gliomagenic hibernation following T11TS therapy. In the present study, we investigated the impact of glioma on canonical wnt and notch signaling cascades followed by exploration gliomagenic fate of both myeloid and lymphoid progenitors within bone marrow compartment and the consequences following T11TS therapy. Flowcytometry, immunoblotting, and immunofluorescence imagining results revealed multipotent T11TS not only significantly up-regulates gliomagenic under expression of Wnt-1 and Notch-1 but also strongly reactivates the expression of Frizzled-1, ß-catenin, and Jagged-1, the respective downstream mediators to impart their regulatory effect on glioma associated BMHSCs. T11TS is also able to up-modulates both the key myeloid (CD123, CD38) and Lymphoid (CD127, Flt-3) progenitors cell marker from the gliomagenic downregulation and guide the glioma devastated BMHSCs towards effective regeneration immune system by up-regulation CD2, CD7, CD56, CD19, and CD14 which were otherwise significantly downregulated during ENU mediated glioma progression. These results decipher the crucial insight into how the novel immunomodulatory T11TS counteract gliomagenic immune devastation and facilitated prognosis.
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Add to Calendar ▼2017-09-15 00:00:002017-09-15 00:00:00Europe/LondonCellTech and BioimagingCellTech and Bioimaging in BengaluruBengaluruSELECTBIOenquiries@selectbiosciences.com
