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@ARTICLE{Hahn:186665,
      author       = {A. W. Hahn and A. V. Menk and D. B. Rivadeneira and R. C.
                      Augustin and M. Xu and J. Li and X. Wu and A. K. Mishra and
                      T. N. Gide and C. Quek and Y. Zang and C. N. Spencer and A.
                      M. Menzies and C. R. Daniel and C. W. Hudgens and T. Nowicki
                      and L. E. Haydu and M. A. W. Khan and V. Gopalakrishnan and
                      E. M. Burton and J. Malke and J. M. Simon and C. Bernatchez
                      and N. Putluri and S. E. Woodman and Y. N. Vashisht Gopal
                      and R. Guerrieri and G. M. Fischer and J. Wang and K. M.
                      Wani and J. F. Thompson and J. E. Lee and P. Hwu and N.
                      Ajami and J. E. Gershenwald and G. V. Long and R. A. Scolyer
                      and M. T. Tetzlaff and A. J. Lazar and D. Schadendorf$^*$
                      and J. A. Wargo and J. M. Kirkwood and R. J. DeBerardinis
                      and H. Liang and A. Futreal and J. Zhang and J. S. Wilmott
                      and W. Peng and M. A. Davies and G. M. Delgoffe and Y. G.
                      Najjar and J. L. McQuade},
      title        = {{O}besity {I}s {A}ssociated with {A}ltered {T}umor
                      {M}etabolism in {M}etastatic {M}elanoma.},
      journal      = {Clinical cancer research},
      volume       = {29},
      number       = {1},
      issn         = {1078-0432},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {AACR},
      reportid     = {DKFZ-2023-00034},
      pages        = {154 - 164},
      year         = {2023},
      abstract     = {Overweight/obese (OW/OB) patients with metastatic melanoma
                      unexpectedly have improved outcomes with immune checkpoint
                      inhibitors (ICI) and BRAF-targeted therapies. The
                      mechanism(s) underlying this association remain unclear,
                      thus we assessed the integrated molecular, metabolic, and
                      immune profile of tumors, as well as gut microbiome
                      features, for associations with patient body mass index
                      (BMI).Associations between BMI [normal (NL < 25) or OW/OB
                      (BMI ≥ 25)] and tumor or microbiome characteristics were
                      examined in specimens from 782 patients with metastatic
                      melanoma across 7 cohorts. DNA associations were evaluated
                      in The Cancer Genome Atlas cohort. RNA sequencing from 4
                      cohorts (n = 357) was batch corrected and gene set
                      enrichment analysis (GSEA) by BMI category was performed.
                      Metabolic profiling was conducted in a subset of patients (x
                      = 36) by LC/MS, and in flow-sorted melanoma tumor cells (x =
                      37) and patient-derived melanoma cell lines (x = 17) using
                      the Seahorse XF assay. Gut microbiome features were examined
                      in an independent cohort (n = 371).DNA mutations and copy
                      number variations were not associated with BMI. GSEA
                      demonstrated that tumors from OW/OB patients were
                      metabolically quiescent, with downregulation of oxidative
                      phosphorylation and multiple other metabolic pathways.
                      Direct metabolite analysis and functional metabolic
                      profiling confirmed decreased central carbon metabolism in
                      OW/OB metastatic melanoma tumors and patient-derived cell
                      lines. The overall structure, diversity, and taxonomy of the
                      fecal microbiome did not differ by BMI.These findings
                      suggest that the host metabolic phenotype influences
                      melanoma metabolism and provide insight into the improved
                      outcomes observed in OW/OB patients with metastatic melanoma
                      treated with ICIs and targeted therapies. See related
                      commentary by Smalley, p. 5.},
      subtyp        = {Editorial},
      keywords     = {Humans / Risk Factors / DNA Copy Number Variations /
                      Obesity: complications / Overweight / Melanoma: genetics /
                      Melanoma: complications / Body Mass Index / Neoplasms,
                      Second Primary},
      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:36166093},
      doi          = {10.1158/1078-0432.CCR-22-2661},
      url          = {https://inrepo02.dkfz.de/record/186665},
}