Th-1 polarization is regulated by dendritic-cell comparison of MHC class I and class II antigens

Chemo-immunotherapy mediates durable cure of orthotopic KrasG12D/p53−/−pancreatic ductal adenocarcinoma

“…All analyses were performed on purified DC that had no previous or subsequent contact with T-cell populations as described previously. 16 These results confirmed that homologous antigenic loading of DC with PDAC antigens could recapitulate the previously characterized T H 1 polarizing phenotype.…”

“…¡/¡ luc2 neg cells, matured, and analyzed for previously described hallmarks [16][17][18] of homologous antigenic loading. Also as described previously, [16][17][18] DC were loaded singly with PDAC mRNA, singly with PDAC cell lysate, and doubly in a heterologous fashion with PDAC mRNA and irrelevant B16 tumor lysate to serve as comparative controls.…”

“…Also as described previously, [16][17][18] DC were loaded singly with PDAC mRNA, singly with PDAC cell lysate, and doubly in a heterologous fashion with PDAC mRNA and irrelevant B16 tumor lysate to serve as comparative controls. Western blot of the DC lysates probed with AIMp1 antibody indicated that only homologous antigenic loading resulted in significantly elevated levels of AIMp1 production (Fig.…”

“…DC loaded in this manner also demonstrate a substantial reorganization of the transcriptome, exhibiting a transcriptional profile significantly different from alternatively loaded DC by over 1,700 transcripts in areas such as interferon signaling, antigen-presentation, antiviral responses, protein ubiquitination, and DC licensing. [16][17][18] Using nearly 40 different independent antigenic systems, previous work demonstrated that loading of DC MHC class I and II with antigens of similar or identical content stimulates release of the T H 1-promoting cytokine AIMp1/p43 with concomitant reduction in the release of CTLA-4 C regulatory microvesicles, and that these events are not dependent on innate pattern recognition or TLR ligands. 18 This concept has subsequently been utilized for the generation of cell-based vaccine platforms that specifically target cancer with highly cytotoxic T-cell responses of durable memory potential.…”

Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy

“…One way to overcome this is to combine different antigen-loading methods (e.g., pulsing with lysates in conjunction with mRNA loading) to allow the antigen(s) to access both the MHC class I-and II-processing pathways (Decker et al, 2009;Decker et al, 2006). Another appealing strategy is to use tumor antigen-encoding mRNA that is appended with an MHC class II-targeting sequence of an endosomal/lysosomal protein, such as DClysosome-associated membrane protein .…”