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@ARTICLE{Prakash:130352,
      author       = {H. Prakash$^*$ and F. Klug$^*$ and V. Nadella and V.
                      Mazumdar and H. Schmitz-Winnenthal and L. Umansky},
      title        = {{L}ow doses of gamma irradiation potentially modifies
                      immunosuppressive tumor microenvironment by retuning
                      tumor-associated macrophages: lesson from insulinoma.},
      journal      = {Carcinogenesis},
      volume       = {37},
      number       = {3},
      issn         = {1460-2180},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2017-05431},
      pages        = {301 - 313},
      year         = {2016},
      abstract     = {Tumor infiltrating iNOS+ macrophages under the influence of
                      immunosuppressive tumor microenvironment gets polarized to
                      tumor-promoting and immunosuppressive macrophages, known as
                      tumor-associated macrophages (TAM). Their recruitment and
                      increased density in the plethora of tumors has been
                      associated with poor prognosis in cancer patients.
                      Therefore, retuning of TAM to M1 phenotype would be a key
                      for effective immunotherapy. Radiotherapy has been a
                      potential non-invasive strategy to improve cancer
                      immunotherapy and tumor immune rejection. Irradiation of
                      late-stage tumor-bearing Rip1-Tag5 mice twice with 2 Gy dose
                      resulted in profound changes in the inflammatory tumor
                      micromilieu, characterized by induction of M1-associated
                      effecter cytokines as well as reduction in protumorigenic
                      and M2-associated effecter cytokines. Similarly, in vitro
                      irradiation of macrophages with 2 Gy dose-induced expression
                      of iNOS, NO, NFκBpp65, pSTAT3 and proinflammatory cytokines
                      secretion while downregulating p38MAPK which are involved in
                      iNOS translation and acquisition of an M1-like phenotype.
                      Enhancement of various M2 effecter cytokines and angiogenic
                      reprogramming in iNOs+ macrophage depleted tumors and their
                      subsequent reduction by 2 Gy dose in Rip1-Tag5 transgenic
                      mice furthermore demonstrated a critical role of peritumoral
                      macrophages in the course of gamma irradiation mediated M1
                      retuning of insulinoma.},
      keywords     = {Cytokines (NLM Chemicals)},
      cin          = {G808},
      ddc          = {610},
      cid          = {I:(DE-He78)G808-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26785731},
      doi          = {10.1093/carcin/bgw007},
      url          = {https://inrepo02.dkfz.de/record/130352},
}