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@ARTICLE{Budczies:141992,
      author       = {J. Budczies$^*$ and A. Seidel and P. Christopoulos and V.
                      Endris and M. Kloor$^*$ and B. Győrffy and B. Seliger and
                      P. Schirmacher$^*$ and A. Stenzinger$^*$ and C. Denkert$^*$},
      title        = {{I}ntegrated analysis of the immunological and genetic
                      status in and across cancer types: impact of mutational
                      signatures beyond tumor mutational burden.5},
      journal      = {OncoImmunology},
      volume       = {7},
      number       = {12},
      issn         = {2162-402X},
      address      = {Abingdon},
      publisher    = {Taylor $\&$ Franics},
      reportid     = {DKFZ-2018-02222},
      pages        = {e1526613 -},
      year         = {2018},
      abstract     = {Harnessing the immune system by checkpoint blockade has
                      greatly expanded the therapeutic options for advanced
                      cancer. Since the efficacy of immunotherapies is influenced
                      by the molecular make-up of the tumor and its crosstalk with
                      the immune system, comprehensive analysis of genetic and
                      immunologic tumor characteristics is essential to gain
                      insight into mechanisms of therapy response and resistance.
                      We investigated the association of immune cell contexture
                      and tumor genetics including tumor mutational burden (TMB),
                      copy number alteration (CNA) load, mutant allele
                      heterogeneity (MATH) and specific mutational signatures
                      (MutSigs) using TCGA data of 5722 tumor samples from 21
                      cancer types. Among all genetic variables, MutSigs
                      associated with DNA repair deficiency and AID/APOBEC gene
                      activity showed the strongest positive correlations with
                      immune parameters. For smoking-related and UV-light-exposure
                      associated MutSigs a few positive correlations were
                      identified, while MutSig 1 (clock-like process) correlated
                      non-significantly or negatively with the major immune
                      parameters in most cancer types. High TMB was associated
                      with high immune cell infiltrates in some but not all cancer
                      types, in contrast, high CNA load and high MATH were mostly
                      associated with low immune cell infiltrates. While a bi- or
                      multimodal distribution of TMB was observed in colorectal,
                      stomach and endometrial cancer where its levels were
                      associated with POLE/POLD1 mutations and MSI status, TMB was
                      unimodal distributed in the most other cancer types
                      including NSCLC and melanoma. In summary, this study
                      uncovered specific genetic-immunology associations in major
                      cancer types and suggests that mutational signatures should
                      be further investigated as interesting candidates for
                      response prediction beyond TMB.},
      cin          = {G105},
      ddc          = {610},
      cid          = {I:(DE-He78)G105-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30524909},
      pmc          = {pmc:PMC6279340},
      doi          = {10.1080/2162402X.2018.1526613},
      url          = {https://inrepo02.dkfz.de/record/141992},
}