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@ARTICLE{Liang:303228,
      author       = {Y. Liang$^*$ and L. Mai$^*$ and J. Schneeweiss$^*$ and R.
                      Lopez Perez$^*$ and M. Kirschfink and P. Huber$^*$},
      title        = {{R}adiotherapy {U}pregulates the {E}xpression of
                      {M}embrane-{B}ound {N}egative {C}omplement {R}egulator
                      {P}roteins on {T}umor {C}ells and {L}imits
                      {C}omplement-{M}ediated {T}umor {C}ell {L}ysis.},
      journal      = {Cancers},
      volume       = {17},
      number       = {14},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2025-01579},
      pages        = {2383},
      year         = {2025},
      note         = {#EA:E055#LA:E055#},
      abstract     = {Background/Objectives: Radiotherapy (RT) is a mainstay of
                      clinical cancer therapy that causes broad immune responses.
                      The complement system is a pivotal effector mechanism in the
                      innate immune response, but the impact of RT is less well
                      understood. This study investigates the interaction between
                      RT and the complement system as a possible approach to
                      improve immune responses in cancer treatment. Methods: Human
                      solid cancer (lung, prostate, liver, breast cancer),
                      lymphoma, and leukemia cells were irradiated using X-rays
                      and treated with polyclonal antibodies or anti-CD20
                      monoclonal antibodies, respectively. Chromium release assay
                      was applied to measure cell lysis after radiation with or
                      without complement-activating antibody treatment. The
                      expression of membrane-bound complement regulatory proteins
                      (mCRPs; CD46, CD55, CD59), which confer resistance against
                      complement activation, CD20 expression, apoptosis, and
                      radiation-induced DNA double-strand breaks (γH2AX), was
                      measured by flow cytometry. The radiosensitivity of tumor
                      cells was assessed by colony-forming assay. Results: We
                      demonstrate that RT profoundly impacts complement function
                      by upregulating the expression of membrane-bound complement
                      regulatory proteins (mCRPs) on tumor cells in a dose- and
                      time-dependent manner. Impaired complement-mediated tumor
                      cell lysis could thus potentially contribute to
                      radiotherapeutic resistance. We also observed RT-induced
                      upregulation of CD20 expression on lymphoma and leukemic
                      cells. Notably, complement activation prior to RT proved
                      more effective in inducing RT-dependent early apoptosis
                      compared to post-irradiation treatment. While complement
                      modulation does not significantly alter RT-induced
                      DNA-damage repair mechanisms or intrinsic radiosensitivity
                      in cancer cells, our results suggest that combining RT with
                      complement-based anti-cancer therapy may enhance
                      complement-dependent cytotoxicity (CDC) and apoptosis in
                      tumor cells. Conclusions: This study sheds light on the
                      complex interplay between RT and the complement system,
                      offering insights into potential novel combinatorial
                      therapeutic strategies and a potential sequential structure
                      for certain tumor types.},
      keywords     = {CD20 (Other) / DNA-damage repair (Other) / complement
                      activation (Other) / complement-dependent cytotoxicity (CDC)
                      (Other) / membrane-bound complement regulatory proteins
                      (mCRPs) (Other) / radiosensitivity (Other) / radiotherapy
                      (Other) / timing (Other)},
      cin          = {E055},
      ddc          = {610},
      cid          = {I:(DE-He78)E055-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40723265},
      doi          = {10.3390/cancers17142383},
      url          = {https://inrepo02.dkfz.de/record/303228},
}