Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
STAT3 knockdown in B16 melanoma by siRNA lipopolyplexes induces bystander immune response in vitro and in vivo
Translational Oncology, Volume 4, No. 3, Year 2011
Notification
URL copied to clipboard!
Description
Persistent activation of STAT3 plays a major role in cancer progression and immune escape. Therefore, targeting STAT3 in tumors is essential to enhance/reactivate antitumor immune response. In our previous studies, we demonstrated the efficacy of stearic acid-modified polyethylenimine (PEI-StA) in promoting small interfering RNA (siRNA) silencing of STAT3 in B16.F10 melanoma in vitro and in vivo. In the current study, we examine the immunologic impact of this intervention. Toward this goal, the infiltration and activation of lymphocytes and dendritic cells (DCs) in the tumor mass were assessed using flow cytometry. Moreover, the levels of IFN-γ, IL-12, and TNF-α in homogenized tumor supernatants were determined. Moreover, mixed lymphocytes reaction using splenocytes of tumorbearing mice was used to assess DC functionality on siRNA/lipopolyplexes intervention. Our results demonstrated up to an approximately fivefold induction in the infiltration of CD3+ cells in tumor mass on STAT3 knockdown with high levels of CD4+, CD8+, and NKT cells. Consistently, DC infiltration in tumor milieu increased up to approximately fourfold. Those DCs were activated, in an otherwise suppressive microenvironment, as evidenced by a high expression of costimulatory molecules CD86 and CD40. ELISA analysis revealed a significant increase in IFN-γ, IL-12, and TNF-α. Moreover, mixed lymphocytes reaction demonstrated alloreactivity of these DCs as assessed by high T-cell proliferation and IL-2 production. Our results suggest a bystander immune response after local STAT3 silencing by siRNA. This strategy could be beneficial as an adjuvant therapy along with current cancer vaccine formulations. © 2011 Neoplasia Press, Inc. All rights reserved.
Authors & Co-Authors
Alshamsan, Aws
Saudi Arabia, Riyadh
College of Pharmacy
Canada, Edmonton
University of Alberta
Hamdy, Samar
Canada, Edmonton
University of Alberta
Haddadi, Azita
Canada, Saskatoon
University of Saskatchewan
Samuel, John
Canada, Edmonton
University of Alberta
El-Kadi, Ayman O.S.
Canada, Edmonton
University of Alberta
Uludaǧ, Hasan
Canada, Edmonton
University of Alberta
Lavasanifar, Afsaneh
Canada, Edmonton
University of Alberta
Statistics
Citations: 32
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1593/tlo.11100
e-ISSN:
19365233
Research Areas
Cancer
Study Design
Randomised Control Trial