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T cell mediated immunosuppression contributes to the progression of NF1 associated tumors in the PNF & NPcis mouse model

Thursday, September 13, 2018 — Poster Session III

12:00 p.m. – 1:30 p.m.
FAES Terrace
NCI
IMMUNO-15

Authors

  • S Karmakar
  • RG Tuskan
  • K Pendo
  • I Shetty
  • BC Widemann
  • KM Reilly

Abstract

Neurofibromatosis type I affects 1 individual in 3500. NF1 mutation leads to tumors in nerves that can progress to malignant peripheral nerve sheath tumors (MPNST). Despite much effort to develop therapeutic strategies, currently there are no therapies available to prevent growth and progression of MPNST. How the immune system is affected by Nf1 mutation and therefore enhances MPNST progression has not been fully elucidated yet. Unleashing the cytotoxic ability of the immune system to fight MPNSTs could be crucial for the development of a potent immunotherapy in MPNST patients. In our current study, we are evaluating the immune-regulatory responses in the PBMCs and splenocytes of a Nf1-/+;Trp53-/+cis (NPcis) mouse model. Current focus is on how the Nf1-specific alteration in immunoregulation can be involved in progressing MPNST. Cancer immunotherapy has recently emerged as an innovative therapeutic option. Here we have established the correlation between various markers such as CTLA-4, PD-1, CD25, CD69, FoxP3, IFN-γ, TNF-α, IL-10, TGF-β and CXCR4 with MPNST progression through flow-cytometry, qPCR and cytokine ELISA methods. Detection of markers in the NF1 patients will provide more clarity about the status of the MPNST patient and proper immunotherapeutic intervention to treat MPNST. We are evaluating the Nf1 specific immunoregulation by analyzing immune regulatory markers in Nf1-/+ mice and Plexiform Neurofibromatosis (PNF), a benign form of nerve sheath tumor. Significant changes in some immune regulatory markers in MPNST mice prompted us to hypothesize that Nf1 mutation affects immune regulation through altering T cell characteristics leading to the progression of MPNST. We have established mouse syngraft MPNST models in a B6 wt and B6 Nf1-/+ background. We believe that this model will elucidate how the role of T cell mediated immune responses are altered by NF1 mutation in MPNST patients. We will present here the results of our ongoing analysis.

Category: Immunology