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Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy

Jiménez-Sánchez, Alejandro ; Cybulska, Paulina ; Mager, Katherine LaVigne ; Koplev, Simon ; Cast, Oliver ; Couturier, Dominique-Laurent ; Memon, Danish ; Selenica, Pier ; Nikolovski, Ines ; Mazaheri, Yousef ; Bykov, Yonina ; Geyer, Felipe C ; Macintyre, Geoff ; Gavarró, Lena Morrill ; Drews, Ruben M ; Gill, Michael B ; Papanastasiou, Anastasios D ; Sosa, Ramon E ; Soslow, Robert A ; Walther, Tyler ; Shen, Ronglai ; Chi, Dennis S ; Park, Kay J ; Hollmann, Travis ; Reis-Filho, Jorge S ; Markowetz, Florian ; Beltrao, Pedro ; Vargas, Hebert Alberto ; Zamarin, Dmitriy ; Brenton, James D ; Snyder, Alexandra ; Weigelt, Britta ; Sala, Evis ; Miller, Martin L

Nature genetics, 2020-06, Vol.52 (6), p.582-593 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy
Autor: Jiménez-Sánchez, Alejandro ; Cybulska, Paulina ; Mager, Katherine LaVigne ; Koplev, Simon ; Cast, Oliver ; Couturier, Dominique-Laurent ; Memon, Danish ; Selenica, Pier ; Nikolovski, Ines ; Mazaheri, Yousef ; Bykov, Yonina ; Geyer, Felipe C ; Macintyre, Geoff ; Gavarró, Lena Morrill ; Drews, Ruben M ; Gill, Michael B ; Papanastasiou, Anastasios D ; Sosa, Ramon E ; Soslow, Robert A ; Walther, Tyler ; Shen, Ronglai ; Chi, Dennis S ; Park, Kay J ; Hollmann, Travis ; Reis-Filho, Jorge S ; Markowetz, Florian ; Beltrao, Pedro ; Vargas, Hebert Alberto ; Zamarin, Dmitriy ; Brenton, James D ; Snyder, Alexandra ; Weigelt, Britta ; Sala, Evis ; Miller, Martin L
Assuntos: Animals ; Biotechnology industry ; Cancer ; Cancer therapies ; Case studies ; Chemotherapy ; Cisplatin - immunology ; Cisplatin - pharmacology ; Cohort Studies ; Copy number ; Cystadenocarcinoma, Serous - drug therapy ; Cystadenocarcinoma, Serous - genetics ; Cystadenocarcinoma, Serous - immunology ; Deoxyribonucleic acid ; DNA ; DNA Copy Number Variations ; Female ; Gene expression ; Gene Expression Profiling - statistics & numerical data ; Gene Expression Regulation, Neoplastic - drug effects ; Genes ; Genes, myc ; Genetic aspects ; Genomics ; Heterogeneity ; Humans ; Immune system ; Immunogenicity ; Infiltration ; Inflammation ; Killer Cells, Natural - drug effects ; Lymphocytes ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - pathology ; Metastases ; Metastasis ; Mice ; Microenvironments ; Mutation ; Myc protein ; Natural killer cells ; Ovarian cancer ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - immunology ; Patients ; Principal Component Analysis ; T cells ; Tumor Microenvironment - drug effects ; Tumor Microenvironment - genetics ; Tumor Microenvironment - immunology ; Tumors ; Wnt protein ; Wnt Signaling Pathway
É parte de: Nature genetics, 2020-06, Vol.52 (6), p.582-593
Notas: Methodology [Development or design of methodology; creation of models]
A.J.-S., D.-L.C., R.M.D., O.C.
Conceptualization [Ideas; formulation or evolution of overarching research goals and aims] A.J.-S., A.S., E.S., M.L.M.
A.J.-S., K.L.M., P.C., S.K., O.C., P.S.
H.A.V., B.W., J.S.R.-F., D.Z., E.S., A.S., M.L.M.
Software [Programming, software development; designing computer programs, implementation of the computer code and supporting algorithms; testing of existing code components]
P.C., K.L.M., T.W., Y.M., Y.B., I.N., J.S.R.-F., P.B., B.W., T.H., K.J.P., D.S.C., R.S., E.S., F.C.G., A.D.P., R.A.S., R.E.S., P.S.
Project administration [Management and coordination responsibility for the research activity planning and execution]
A.J.-S., E.S.
Funding acquisition [Acquisition of the financial support for the project leading to this publication]
Formal analysis [Application of statistical, mathematical, computational, or other formal techniques to analyse or synthesize study data]
Investigation [Conducting a research and investigation process, specifically performing the experiments, or data/evidence collection]
A.J.-S., A.S., E.S., M.L.M.
CRediT standard taxonomy http://dictionary.casrai.org/Contributor_Roles
A.J.-S., D.-L.C., S.K., O.C., P.S., D.M.
Resources [Provision of study materials, reagents, materials, patients, laboratory samples, animals, instrumentation, computing resources, or other analysis tools]
Data curation [Management activities to annotate (produce metadata), scrub data and maintain research data (including software code, where necessary for interpreting the data itself) for initial use and later re-use]
A.J.-S., A.S., M.L.M.
A.J.-S., S.K., D.-L.C., O.C.
AUTHOR CONTRIBUTIONS
Supervision [Oversight and leadership responsibility for the research activity planning and execution, including mentorship external to the core team]
A.S., J.S.R.-F., B.W., E.S., M.L.M.
Writing original draft [Preparation, creation and/or presentation of the published work, specifically writing the initial draft]
A.S., J.S.R.-F., B.W., D.S.C., D.Z., M.L.M., E.S.
Writing review & editing [Preparation, creation and/or presentation of the published work by those from the original research group, specifically critical review, commentary or revision] A.J.-S., M.L.M., A.S., K.L.M., P.C., E.S., J.D.B., M.B.G., L.M.G., G.M., R.M.D., B.W., J.S.R.-F., S.K., F.M., P.B., O.C., D.-L.C.
Visualization [Preparation, creation and/or presentation of the published work, specifically visualization/data presentation]
A.J.-S., D.-L.C., S.K., O.C., R.M.D., L.M.G., G.M.
Validation [Verification, whether as a part of the activity or separate, of the overall replication/reproducibility of results/experiments and other research outputs]
Descrição: In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following NACT, increased natural killer (NK) cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor-immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy

United States: Nature Publishing Group

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