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Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient.

Abstract We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8(+) and CD4(+) T cells and exhibited oligoclonal expansion of specific T cell subsets. We also detected CD8(+) T cell reactivity against predicted neoepitopes after isolation of cells from a blood sample taken almost 3 years after the tumors were resected. These findings suggest that multiple distinct tumor immune microenvironments co-exist within a single individual and may explain in part the heterogeneous fates of metastatic lesions often observed in the clinic post-therapy. VIDEO ABSTRACT.
PMID
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Authors

Mayor MeshTerms

Tumor Microenvironment

Keywords
Journal Title cell
Publication Year Start




PMID- 28841418
OWN - NLM
STAT- MEDLINE
DA  - 20170825
DCOM- 20170901
LR  - 20170901
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Linking)
VI  - 170
IP  - 5
DP  - 2017 Aug 24
TI  - Heterogeneous Tumor-Immune Microenvironments among Differentially Growing
      Metastases in an Ovarian Cancer Patient.
PG  - 927-938.e20
LID - S0092-8674(17)30832-2 [pii]
LID - 10.1016/j.cell.2017.07.025 [doi]
AB  - We present an exceptional case of a patient with high-grade serous ovarian
      cancer, treated with multiple chemotherapy regimens, who exhibited regression of 
      some metastatic lesions with concomitant progression of other lesions during a
      treatment-free period. Using immunogenomic approaches, we found that progressing 
      metastases were characterized by immune cell exclusion, whereas regressing and
      stable metastases were infiltrated by CD8+ and CD4+ T cells and exhibited
      oligoclonal expansion of specific T cell subsets. We also detected CD8+ T cell
      reactivity against predicted neoepitopes after isolation of cells from a blood
      sample taken almost 3 years after the tumors were resected. These findings
      suggest that multiple distinct tumor immune microenvironments co-exist within a
      single individual and may explain in part the heterogeneous fates of metastatic
      lesions often observed in the clinic post-therapy. VIDEO ABSTRACT.
CI  - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Jimenez-Sanchez, Alejandro
AU  - Jimenez-Sanchez A
AD  - Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing
      Centre, Robinson Way, Cambridge CB2 0RE, UK.
FAU - Memon, Danish
AU  - Memon D
AD  - Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing
      Centre, Robinson Way, Cambridge CB2 0RE, UK; European Molecular Biology
      Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus,
      Hinxton, Cambridge CB10 1SD, UK.
FAU - Pourpe, Stephane
AU  - Pourpe S
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue,
      New York, NY 10065, USA.
FAU - Veeraraghavan, Harini
AU  - Veeraraghavan H
AD  - Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York 
      Avenue, New York, NY 10065, USA.
FAU - Li, Yanyun
AU  - Li Y
AD  - Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering
      Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
FAU - Vargas, Hebert Alberto
AU  - Vargas HA
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York
      Avenue, New York, NY 10065, USA.
FAU - Gill, Michael B
AU  - Gill MB
AD  - Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing
      Centre, Robinson Way, Cambridge CB2 0RE, UK.
FAU - Park, Kay J
AU  - Park KJ
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York
      Avenue, New York, NY 10065, USA.
FAU - Zivanovic, Oliver
AU  - Zivanovic O
AD  - Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer
      Center, 1275 York Avenue, New York, NY 10065, USA.
FAU - Konner, Jason
AU  - Konner J
AD  - Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan
      Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
FAU - Ricca, Jacob
AU  - Ricca J
AD  - Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering
      Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
FAU - Zamarin, Dmitriy
AU  - Zamarin D
AD  - Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering
      Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Department of Medicine,
      Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065,
      USA.
FAU - Walther, Tyler
AU  - Walther T
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue,
      New York, NY 10065, USA.
FAU - Aghajanian, Carol
AU  - Aghajanian C
AD  - Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan
      Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
FAU - Wolchok, Jedd D
AU  - Wolchok JD
AD  - Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering
      Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Parker Institute for
      Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, 1275 York Avenue,
      New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, 1275 York Avenue, New York, NY 10065, USA; Department of Medicine, Weill 
      Cornell Medical College, New York, NY, USA; Immunology and Microbial Pathogenesis
      Programs, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, 
      USA.
FAU - Sala, Evis
AU  - Sala E
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York
      Avenue, New York, NY 10065, USA.
FAU - Merghoub, Taha
AU  - Merghoub T
AD  - Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering
      Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
FAU - Snyder, Alexandra
AU  - Snyder A
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue,
      New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College,
      New York, NY, USA. Electronic address: [email protected]
FAU - Miller, Martin L
AU  - Miller ML
AD  - Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing
      Centre, Robinson Way, Cambridge CB2 0RE, UK. Electronic address:
      [email protected]
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Antigens, Neoplasm)
SB  - IM
MH  - Antigens, Neoplasm/immunology
MH  - Cystadenocarcinoma, Serous/genetics/immunology/*pathology/therapy
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mutation
MH  - Neoplasm Metastasis/genetics/*immunology/therapy
MH  - Ovarian Neoplasms/genetics/immunology/*pathology/therapy
MH  - T-Lymphocytes/immunology
MH  - Transcriptome
MH  - *Tumor Microenvironment
EDAT- 2017/08/26 06:00
MHDA- 2017/09/02 06:00
CRDT- 2017/08/26 06:00
PHST- 2016/01/12 [received]
PHST- 2017/06/06 [revised]
PHST- 2017/07/14 [accepted]
AID - S0092-8674(17)30832-2 [pii]
AID - 10.1016/j.cell.2017.07.025 [doi]
PST - ppublish
SO  - Cell. 2017 Aug 24;170(5):927-938.e20. doi: 10.1016/j.cell.2017.07.025.