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@ARTICLE{Nelson:294365,
author = {B. H. Nelson and P. T. Hamilton and M. T. Phung and K.
Milne and B. Harris and S. Thornton and D. L. Stevens and S.
Kalaria and K. Singh and C. M. Laumont and E. Moss and A.
Alimujiang and N. S. Meagher and A. Bolithon and S. Fereday
and C. J. Kennedy and J. Hendley and D. Ariyaratne and K.
Alsop and N. Traficante and E. L. Goode and A. N. Karnezis
and H. Shen and J. Richardson and C. McKinnon Deurloo and A.
Chase and B. Grout and J. A. Doherty and H. R. Harris and K.
L. Cushing-Haugen and M. S. Anglesio and K. Heinze and D.
Huntsman and A. Talhouk and G. E. Hanley and J. Alsop and M.
Jimenez-Linan and P. D. Pharoah and J. Boros and A. H. Brand
and P. R. Harnett and R. Sharma and J. L. Hecht and N.
Sasamoto and K. L. Terry and B. Y. Karlan and J. Lester and
M. E. Carney and M. T. Goodman and B. Y. Hernandez and L. R.
Wilkens and S. Behrens$^*$ and R. Turzanski Fortner$^*$ and
P. A. Fasching and C. Bisinotto and F. J. Candido Dos Reis
and P. Ghatage and M. Köbel and E. Elishaev and F. Modugno
and L. S. Cook and N. D. Le and A. Gentry-Maharaj and U.
Menon and M. J. García and C. Rodriguez-Antona and K. M.
Farrington and L. E. Kelemen and S. Kommoss and A. Staebler
and D. W. Garsed and J. D. Brenton and A. M. Piskorz and D.
D. Bowtell and A. DeFazio and S. J. Ramus and M. C. Pike and
C. L. Pearce},
title = {{I}mmunological and molecular features of the tumor
microenvironment of long-term survivors of ovarian cancer.},
journal = {The journal of clinical investigation},
volume = {134},
number = {24},
issn = {0021-9738},
address = {Ann Arbor, Mich.},
publisher = {ASCJ},
reportid = {DKFZ-2024-02198},
pages = {e179501},
year = {2024},
note = {2024 Oct 29;134(24):e179501},
abstract = {Despite an overall poor prognosis, about $15\%$ of patients
with advanced-stage tubo-ovarian high-grade serous carcinoma
(HGSC) survive ten or more years after standard treatment.We
evaluated the tumor microenvironment of this exceptional,
understudied group using a large international cohort
enriched for long-term survivors (LTS; 10+ years; n = 374)
compared to medium-term (MTS; 5-7.99 years; n = 433) and
short-term survivors (STS; 2-4.99 years; n = 416). Primary
tumor samples were immunostained and scored for
intra-epithelial and intra-stromal densities of 10
immune-cell subsets (including T cells, B cells, plasma
cells, myeloid cells, PD-1+ cells, and PD-L1+ cells) and
epithelial content.Positive associations with LTS compared
to STS were seen for 9/10 immune-cell subsets. In
particular, the combination of intra-epithelial CD8+ T cells
and intra-stromal B cells showed near five-fold increased
odds of LTS compared to STS. All of these associations were
stronger in tumors with high epithelial content and/or the
C4/Differentiated molecular subtype, despite immune-cell
densities generally being higher in tumors with low
epithelial content and/or the C2/Immunoreactive molecular
subtype.The tumor microenvironment of HGSC long-term
survivors is distinguished by the intersection of T and B
cell co-infiltration, high epithelial content and
C4/Differentiated molecular subtype, features which may
inspire new approaches to immunotherapy.Ovarian Cancer
Research Program (OCRP) of the Congressionally Directed
Medical Research Program (CDMRP), U.S. Department of Defense
(DOD); American Cancer Society; BC Cancer Foundation;
Canada's Networks of Centres of Excellence; Canadian Cancer
Society; Canadian Institutes of Health Research; Cancer
Councils of New South Wales, Victoria, Queensland, South
Australia and Tasmania, Cancer Foundation of Western
Australia; Cancer Institute NSW; Cancer Research UK;
Deutsche Forschungsgesellschaft; ELAN Funds of the
University of Erlangen-Nuremberg; Fred C. and Katherine B.
Andersen Foundation; Genome BC; German Cancer Research
Center; German Federal Ministry of Education and Research,
Programme of Clinical Biomedical Research; Instituto de
Salud Carlos III; Mayo Foundation; Minnesota Ovarian Cancer
Alliance; Ministerio de Economía y Competitividad; MRC;
National Center for Advancing Translational Sciences;
National Health and Medical Research Council of Australia
(NHMRC); Ovarian Cancer Australia; Peter MacCallum
Foundation; Sydney West Translational Cancer Research
Centre; Terry Fox Research Institute; The Eve Appeal (The
Oak Foundation); UK National Institute for Health Research
Biomedical Research Centres at the University of Cambridge;
University of Pittsburgh School of Medicine; U.S. National
Cancer Institute of the National Institutes of Health; VGH
$\&$ UBC Hospital Foundation; Victorian Cancer Agency.},
keywords = {Cancer (Other) / Cellular immune response (Other) /
Epidemiology (Other) / Immunology (Other) / Oncology
(Other)},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39470729},
doi = {10.1172/JCI179501},
url = {https://inrepo02.dkfz.de/record/294365},
}