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Neuropilin‐1 Deficient Macrophages as a Treatment Strategy for Glioblastoma
Author(s) -
Caponegro Michael D.,
Tsirka Stella E.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.510.6
Subject(s) - glioma , microglia , tumor microenvironment , cancer research , neuropilin 1 , stromal cell , immune system , ex vivo , macrophage , immunotherapy , medicine , in vivo , immunology , biology , in vitro , inflammation , vascular endothelial growth factor , biochemistry , microbiology and biotechnology , vegf receptors
Post‐diagnosis survival of grade IV glioblastoma (GB) is a dismal 14 months in patients receiving standard of care therapy. With the development of immunotherapeutic strategies targeting non‐cancerous, stromal cells of the tumor microenvironment (TME), new avenues are being pursued in clinical trials and pre‐clinical animal models of advanced GB. Glioma‐associated microglia/macrophages (GAMs) of the TME promote chemoattraction, immune suppression, neoangiogenesis, and tumor cell survival, which parallels tumor‐infiltrating macrophage behavior of other solid malignancies. GAMs are now recognized as a potentially practical immunotherapeutic target in GB. Previously in our lab, we have shown that GAM‐specific deletion of the cell surface co‐receptor Neuropilin‐1 (NRP1) drastically reduces pro‐tumorigenic behavior of infiltrating microglia and/or macrophages in murine glioma by reducing immunosuppressive tendencies and neoangiogenesis. As an extension to our genetically‐ablated mouse model, we present here a platform by which these NRP1‐deficient monocytic cells can be harvested ex vivo and locally delivered into the TME of the bulk glioma lesion, to exert anti‐tumorigenic effects. To our knowledge, this is the first attempt to deliver cells of monocytic origin intratumorally as a therapeutic option. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .