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@ARTICLE{Handke:284823,
      author       = {A. Handke$^*$ and C. Kesch$^*$ and W. P. Fendler$^*$ and T.
                      Telli$^*$ and Y. Liu and A. Hakansson and E. Davicioni and
                      J. Hughes and H. Song and K. Lueckerath$^*$ and K.
                      Herrmann$^*$ and B. Hadaschik$^*$ and R. Seifert$^*$},
      title        = {{A}nalysing the tumor transcriptome of prostate cancer to
                      predict efficacy of {L}u-{PSMA} therapy.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {11},
      number       = {10},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-02119},
      pages        = {e007354},
      year         = {2023},
      abstract     = {177Lu-PSMA ([177Lu]Lutetium-PSMA-617) therapy is an
                      effective treatment option for patients with prostate
                      specific membrane antigen (PSMA)-positive metastatic
                      castration-resistant prostate cancer, but still shows a
                      non-responder rate of approximately $30\%.$ Combination
                      regimes of programmed death-ligand 1 (PD-L1) inhibition and
                      concomitant 177Lu-PSMA therapy have been proposed to
                      increase the response rate. However, the interplay of immune
                      landscape and 177Lu-PSMA therapy efficacy is poorly
                      understood.Between March 2018 and December 2021, a total of
                      168 patients were referred to 177Lu-PSMA therapy in our
                      department and received a mean total dose of 21.9 GBq (three
                      cycles in mean). All patients received baseline PSMA
                      positron emission tomography to assess the PSMA uptake. The
                      histopathological specimen of the primary prostate tumor was
                      available with sufficient RNA passing quality control steps
                      for genomic analysis in n=23 patients. In this subset of
                      patients, tumor RNA transcriptomic analyses assessed 74
                      immune-related features in total, out of which n=24
                      signatures were not co-correlated and investigated further
                      for outcome prognostication.In the subset of patients who
                      received 177Lu-PSMA therapy, PD-L1 was not significantly
                      associated with OS (HR per SD change $(95\%$ CI) 0.74 (0.42
                      to 1.30); SD: 0.18; p=0.29). In contrast, PD-L2 signature
                      was positively associated with longer OS (HR per SD change
                      0.46 $(95\%$ CI 0.29 to 0.74); SD: 0.24; p=0.001; median OS
                      17.2 vs 5.7 months in higher vs lower PD-L2 patients). In
                      addition, PD-L2 signature correlated with PSA-response
                      (ϱ=-0.46; p=0.04). The PD-L2 signature association with OS
                      was significantly moderated by L-Lactatdehydrogenase (LDH)
                      levels (Cox model interaction p=0.01).Higher PD-L2 signature
                      might be associated with a better response to 177Lu-PSMA
                      therapy and warrants further studies investigating
                      additional immunotherapy. In contrast, PD-L1 was not
                      associated with outcome. The protective effect of PD-L2
                      signature might be present only in men with lower LDH
                      levels.},
      keywords     = {Prostatic Neoplasms (Other) / Radiotherapy (Other) / Tumor
                      Biomarkers (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37857524},
      doi          = {10.1136/jitc-2023-007354},
      url          = {https://inrepo02.dkfz.de/record/284823},
}