% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Wang:284401,
      author       = {L. Wang and R. Luo and K. Onyshchenko$^*$ and G.
                      Niedermann$^*$},
      title        = {{D}oxorubicin {E}nhances the {A}bscopal {E}ffect
                      {D}epending on {T}umor {C}ell {M}itochondrial {DNA} and
                      c{GAS}/{STING}.},
      journal      = {International journal of radiation oncology, biology,
                      physics},
      volume       = {117},
      number       = {2S},
      issn         = {0360-3016},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2023-01990},
      pages        = {S158},
      year         = {2023},
      abstract     = {Localized radiotherapy (RT) can cause a T cell-mediated
                      abscopal effect on non-irradiated tumor lesions, especially
                      in combination with immune checkpoint blockade (ICB).
                      However, this effect is still clinically rare and
                      improvements are highly desirable. We investigated whether
                      triple combination with a low dose of clinically approved
                      liposomal doxorubicin (Doxil) could augment abscopal
                      responses compared with RT+ICB, Doxil+ICB, or RT+Doxil.We
                      used Doxil in combination with RT and αPD1 in two tumor
                      models (B16-CD133 melanoma and MC38 colon carcinoma) with
                      mice bearing two tumors, only one of which was
                      irradiated.Triple therapy with RT, αPD1, and single
                      low-dose Doxil strongly enhanced the RT-induced abscopal
                      effect compared to all double and single treatments in both
                      tumor models (p < 0.05, n = 5-10 mice/group). Complete cures
                      of non-irradiated tumors were mainly observed in
                      triple-treated mice. Triple therapy induced more
                      cross-presenting dendritic cells (DCs) and tumor-specific
                      CD8 T cells than RT/αPD1 and Doxil/αPD1 (p < 0.05, n = 5
                      mice/group), particularly in non-irradiated tumors. CD8 T
                      cell depletion or implanting STING-deficient tumor cells
                      abolished the abscopal effect. By using inhibitors and
                      knockout cells, we show that doxorubicin/Doxil-induced
                      IFNβ1 markedly depended on the cGAS/STING pathway (p <
                      0.05) which drives antitumor CD8 T cell responses through
                      cross-presenting DCs. In mitochondrial DNA (mtDNA)-depleted
                      tumor cells, doxorubicin/Doxil induced less IFNβ1 (p <
                      0.05), the related T cell-recruiting chemokine CXCL10 (p <
                      0.0001), and ATP (p < 0.0001); coincubation with
                      mtDNA-depleted tumor cells strongly reduced IFNβ1 (p <
                      0.01) secretion by DCs. Implantation of mtDNA-depleted tumor
                      cells, particularly at the non-irradiated site,
                      substantially diminished the Doxil-enhanced abscopal effect
                      and tumor infiltration by tumor-specific CD8 T cells (p <
                      0.05).Single low-dose Doxil can substantially enhance the
                      RT-induced abscopal effect, with a strong increase in
                      cross-presenting DCs and CD8 tumor-specific T cells
                      particularly in abscopal tumors compared with RT/αPD1 and
                      Doxil/αPD1. The mtDNA/cGAS/STING/IFN-I axis is important
                      for the immunogenic doxorubicin effects. Our findings may be
                      helpful for the planning of clinical radiochemoimmunotherapy
                      trials in (oligo)metastatic patients.},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37784396},
      doi          = {10.1016/j.ijrobp.2023.06.584},
      url          = {https://inrepo02.dkfz.de/record/284401},
}