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A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer
- Source :
- Clinical Cancer Research, 23(24), 7621-7632. American Association for Cancer Research Inc., Clinical Cancer Research, Clinical Cancer Research, American Association for Cancer Research, 2017, 23 (24), pp.7621-7632. ⟨10.1158/1078-0432.CCR-17-1159⟩, Clinical Cancer Research, 23(24), 7621-7632. AMER ASSOC CANCER RESEARCH
- Publication Year :
- 2017
-
Abstract
- Purpose: Most high-grade serous ovarian cancer (HGSOC) patients develop recurrent disease after first-line treatment, frequently with fatal outcome. This work aims at studying the molecular biology of both primary and recurrent HGSOC. Experimental Design: Gene expression profiles of matched primary and recurrent fresh-frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing. Clustering analyses and pairwise comparison of the profiles between matched samples and subsequent functional alignment were used for the identification of molecular characteristics of HGSOC. Results: Both primary and recurrent HGSOC samples presented predominant gene expression differences in their microenvironment, determined by a panel of genes covering all major pathways of immune activation together with a number of genes involved in the remodeling of extracellular matrix and adipose tissues. Stratifying tumor tissues into immune active and silent groups, we further discovered that although some recurrent tumors shared the same immune status as their primary counterparts, others switched the immune status, either from silent to active or active to silent. Interestingly, genes belonging to the B7-CD28 immune checkpoint family, known for their major role as negative regulators of the immune response, were overexpressed in the immune active tumors. Searching for potential tumor antigens, CEACAM21, a member of the carcinoembryonic antigen family, was found to be significantly overexpressed in immune active tissues in comparison with the silent ones. Conclusions: The results illustrate the complexity of the tumor microenvironment in HGSOC and reveal the molecular relationship between primary and recurrent tumors, which have multiple therapeutic implications. Clin Cancer Res; 23(24); 7621–32. ©2017 AACR.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_treatment
CELL INFILTRATION
Metastasis
Carcinoembryonic antigen
Tumor Microenvironment
Ovarian Neoplasms
Middle Aged
3. Good health
Gene Expression Regulation, Neoplastic
Oncology
Female
Life Sciences & Biomedicine
Adult
INFILTRATING LYMPHOCYTES
CARCINOMA
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
03 medical and health sciences
Immune system
Antigen
SDG 3 - Good Health and Well-being
Antigens, Neoplasm
Cell Line, Tumor
medicine
EXTRACELLULAR-MATRIX
Humans
Oncology & Carcinogenesis
IMMUNOTHERAPY
Aged
Tumor microenvironment
Science & Technology
Sequence Analysis, RNA
Cancer
Immunotherapy
medicine.disease
Immune checkpoint
EVOLUTION
Cystadenocarcinoma, Serous
MESH: Ovarian Neoplasms/genetics
Tumor Microenvironment/immunology
Antigens
PD-L1 EXPRESSION
030104 developmental biology
Immunology
METASTASIS
Cancer research
biology.protein
T-CELLS
Neoplasm Grading
Neoplasm Recurrence, Local
1112 Oncology And Carcinogenesis
RESISTANCE
Subjects
Details
- Language :
- English
- ISSN :
- 10780432 and 15573265
- Volume :
- 23
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....688a953de5c5509aa0a2d94c5640f084