Abstract
A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy.
Highlights
Dendritic cells (DCs) are the most important regulators of naıve cells during the generation of T cell-mediated immune responses, and dendritic cell (DC) are the most potent antigen-presenting cells (APCs) [1]
DCs from WT, TLR22/2, or TLR42/2 mice were stimulated with Rv0652 (0.5 ug/ml), and Rv0652 was detected on the cell surface with Alexa568-conjugated anti-Rv0652 monoclonal antibodies
The capacity for antigen uptake is decreased during DC maturation that occurs after antigen recognition and uptake, a phenomenon that is similar to what is observed after LPS treatment of DCs
Summary
Dendritic cells (DCs) are the most important regulators of naıve cells during the generation of T cell-mediated immune responses, and DCs are the most potent antigen-presenting cells (APCs) [1] Because of their central role in modulating cellular immunity, DCs are promising as potent adjuvants for the induction of tumorspecific helper and cytotoxic T cells in tumor-bearing hosts [2,3]. One possibility is that insufficient numbers of CTLs, the effector cells that are considered optimal for causing tumor regression, are activated in response to vaccination with tumor Ag loaded DCs [12]. To overcome this limitation of DC-based antitumor immunotherapeutic strategies, several factors related to in vitro DC manipulation are important for inducing a powerful immune response. Immunostimulatory adjuvants used to enhance DC maturation are required to generate endogenous CTL responses and tumor elimination
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
