Combination therapy targeting both innate and adaptive immunity improves survival in a pre-clinical model of ovarian cancer.
Adaptive Immunity
/ drug effects
Animals
Antineoplastic Agents, Immunological
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
B7-H1 Antigen
/ antagonists & inhibitors
CD4-Positive T-Lymphocytes
/ drug effects
Carboplatin
/ administration & dosage
Combined Modality Therapy
Female
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Immunity, Innate
/ drug effects
Interleukin-10
/ antagonists & inhibitors
Mice
Molecular Targeted Therapy
Nucleotides, Cyclic
/ administration & dosage
Ovarian Neoplasms
/ drug therapy
Paclitaxel
/ administration & dosage
Survival Analysis
Treatment Outcome
Tumor Microenvironment
/ drug effects
Xenograft Model Antitumor Assays
CD4+ T cells
Cancer immunotherapy
Combination therapy
Innate immunity
Ovarian cancer
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
30 07 2019
30 07 2019
Historique:
received:
06
02
2019
accepted:
27
06
2019
entrez:
1
8
2019
pubmed:
1
8
2019
medline:
25
6
2020
Statut:
epublish
Résumé
Despite major advancements in immunotherapy among a number of solid tumors, response rates among ovarian cancer patients remain modest. Standard treatment for ovarian cancer is still surgery followed by taxane- and platinum-based chemotherapy. Thus, there is an urgent need to develop novel treatment options for clinical translation. Our approach was to analyze the effects of standard chemotherapy in the tumor microenvironment of mice harboring orthotopic, syngeneic ID8-Vegf-Defb29 ovarian tumors in order to mechanistically determine a complementary immunotherapy combination. Specifically, we interrogated the molecular and cellular consequences of chemotherapy by analyzing gene expression and flow cytometry data. These data show that there is an immunosuppressive shift in the myeloid compartment, with increased expression of IL-10 and ARG1, but no activation of CD3 This work highlights the importance of CD4
Sections du résumé
BACKGROUND
Despite major advancements in immunotherapy among a number of solid tumors, response rates among ovarian cancer patients remain modest. Standard treatment for ovarian cancer is still surgery followed by taxane- and platinum-based chemotherapy. Thus, there is an urgent need to develop novel treatment options for clinical translation.
METHODS
Our approach was to analyze the effects of standard chemotherapy in the tumor microenvironment of mice harboring orthotopic, syngeneic ID8-Vegf-Defb29 ovarian tumors in order to mechanistically determine a complementary immunotherapy combination. Specifically, we interrogated the molecular and cellular consequences of chemotherapy by analyzing gene expression and flow cytometry data.
RESULTS
These data show that there is an immunosuppressive shift in the myeloid compartment, with increased expression of IL-10 and ARG1, but no activation of CD3
CONCLUSIONS
This work highlights the importance of CD4
Identifiants
pubmed: 31362778
doi: 10.1186/s40425-019-0654-5
pii: 10.1186/s40425-019-0654-5
pmc: PMC6668091
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
Nucleotides, Cyclic
0
cyclic guanosine monophosphate-adenosine monophosphate
0
Interleukin-10
130068-27-8
Carboplatin
BG3F62OND5
Paclitaxel
P88XT4IS4D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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