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@ARTICLE{Rupp:276387,
      author       = {L. Rupp and A. Resag and V. Potkrajcic and V. Warm and R.
                      Wehner$^*$ and K. Jöhrens$^*$ and H. Bösmüller and F.
                      Eckert and M. Schmitz$^*$},
      title        = {{P}rognostic impact of the post-treatment {T} cell
                      composition and spatial organization in soft tissue sarcoma
                      patients treated with neoadjuvant hyperthermic
                      radio(chemo)therapy.},
      journal      = {Frontiers in immunology},
      volume       = {14},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2023-01084},
      pages        = {1185197},
      year         = {2023},
      abstract     = {Soft tissue sarcomas (STS) form a heterogeneous group of
                      tumors sharing a mesenchymal origin. Despite good local
                      control of the disease, the occurrence of distant metastases
                      often limits survival of STS patients with localized,
                      high-risk tumors of the extremities. Accumulating evidence
                      suggests a central role for the tumor immune
                      microenvironment in determining the clinical outcome and
                      response to therapy. Thus, it has been reported that STS
                      patients with a high immune signature and especially
                      presence of B cells and tertiary lymphoid structures display
                      improved overall survival and response to checkpoint
                      inhibitor treatment. Here, we explored the effect of
                      curative multimodal therapy on the T cell landscape of STS
                      using multiplex immunohistochemistry. We analyzed the
                      phenotype, frequency, and spatial distribution of
                      STS-infiltrating CD8+ T cells by staining for CD8, 4-1BB,
                      Granzyme B, Ki67, PD-1, and LAG-3 as well as CD3+ T helper
                      cells using a panel consisting of CD3, T-bet, GATA3, RORγT,
                      FoxP3, and Ki67. All patients received neoadjuvant
                      radiotherapy plus locoregional hyperthermia with or without
                      chemotherapy. While the treatment-naïve biopsy sample
                      allows an analysis of baseline T cell infiltration levels,
                      both intra- and peritumoral areas of the matched resected
                      tissue were analyzed to assess composition and spatial
                      distribution of the T cell compartment and its therapeutic
                      modulation. Generally, post-treatment tissues displayed
                      lower frequencies of CD3+ and CD8+ T cells. Association with
                      clinical data revealed that higher post-treatment
                      frequencies of peritumoral and intratumoral CD3+ T cells and
                      intratumoral PD-1+ CD8+ T cells were significantly
                      associated with improved disease-free survival (DFS), while
                      these densities had no prognostic significance in the
                      biopsy. Upon spatial analysis, a high ratio of intratumoral
                      to peritumoral CD8+ T cells emerged as an independent
                      prognostic marker for longer DFS. These results indicate
                      that the STS T cell landscape is altered by multimodal
                      therapy and may influence the clinical outcome of patients.
                      An enhanced understanding of the STS immune architecture and
                      its modulation by neoadjuvant therapy may pave the way
                      towards novel treatment modalities and improve the long-term
                      clinical outcome of STS patients.},
      keywords     = {T cells (Other) / chemotherapy (Other) / hyperthermia
                      (Other) / immune microenvironment (Other) / immune
                      modulation (Other) / radiotherapy (Other) / soft tissue
                      sarcoma (Other)},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37261361},
      pmc          = {pmc:PMC10228739},
      doi          = {10.3389/fimmu.2023.1185197},
      url          = {https://inrepo02.dkfz.de/record/276387},
}