% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@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},
}