The exceptional immunostimulatory capacity of DCs makes them potential targets for investigation of cancer immunotherapeutics. We show here in mice that TNF-α–stimulated DC maturation was accompanied by increased expression of OX40 ligand (OX40L), the lack of which resulted in an inability of mature DCs to generate cellular antitumor immunity. Furthermore, intratumoral administration of DCs modified to express OX40L suppressed tumor growth through the generation of tumor-specific cytolytic T cell responses, which were mediated by CD4+ T cells and NKT cells. In the tumors treated with OX40L-expressing DCs, the NKT cell population significantly increased and exhibited a substantial level of IFN-γ production essential for antitumor immunity. Additional studies evaluating NKT cell activation status, in terms of IFN-γ production and CD69 expression, indicated that NKT cell activation by DCs presenting α-galactosylceramide in the context of CD1d was potentiated by OX40 expression on NKT cells. These results show a critical role for OX40L on DCs, via binding to OX40 on NKT cells and CD4+ T cells, in the induction of antitumor immunity in tumor-bearing mice.
Jamal Zaini, Sita Andarini, Minoru Tahara, Yasuo Saijo, Naoto Ishii, Kazuyoshi Kawakami, Masaru Taniguchi, Kazuo Sugamura, Toshihiro Nukiwa, Toshiaki Kikuchi
Usage data is cumulative from September 2023 through September 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 598 | 52 |
112 | 30 | |
Figure | 173 | 14 |
Supplemental data | 29 | 1 |
Citation downloads | 31 | 0 |
Totals | 943 | 97 |
Total Views | 1,040 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.