2001 Fiscal Year Final Research Report Summary
An analysis for mechanism of antitumor effects of IL-18 and a clinical application of IL-18 for head and neck tumors
| Project/Area Number |
12671921
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Surgical dentistry
|
|---|
| Research Institution | TOHOKU UNIVERSITY |
|---|
Principal Investigator |
ECHIGO Seishi Graduate School of Dentistry, Tohoku University, Professor, 大学院・歯学研究科, 教授 (70005114)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Wataru Dental Hospital, Tohoku University, Assistant Professor, 歯学部・附属病院, 助手 (30323033)
MORIKAWA Hidehiro Graduate School of Dentistry, Tohoku University, Assistant Professor, 大学院・歯学研究科, 助手 (60302155)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Keywords | IL-18 / antitumor effect / NK cells / IFN-γ / IL-12 / dendritic cells / innate immunity / specific immunity |
|---|
| Research Abstract |
To clarify the antitumor effects of interleukin 18 (IL-18), an effector mechanism of IL-18 was analyzed in murine tumor model. We revealed that NK cells but not NKT cells play a necessary role to promote an innate antitumor response induced by IL-18. Moreover, we hypothesized that antitumor-specific immunity, which is induced by IL-18 treatment in murine tumor models, is promoted by enhancing NK-mediated destruction of tumor and delivery to dendritic cells (DCs). We assesed the effect of IL-18 added to cultures of live tumor cells, NK cells, DCs, and T cells and revealed that IL-18 induces tumor-specific immunity through enhancing NK activity, which in turn mediates tumor cell death and activates and primes DCs.
Next, we investigated the in vitro effects of combining IL-18 and IL-2 on human lymphocytes. The combined use of these two cytokines synergistically enhanced IFN-γ production. Phenotypic analysis revealed a preferential expansion of CD56+ CD3- (NK) cells. To reveal that human lymphocytes activated by IL-18 induce tumor apoptosis, tumor cells were stained with Annexin-V, PhiPhiLux, or PI after 8 hours culture with lymphocytes activated by IL-18. Apoptosis of tumor cells were observed on combined use of these cytokines. These results revealed that IL-18 induces antitumor effects in human system. Therefore, the combined use of IL-2 and IL-18 should be considered a voable strategy for the generation of antitumor responses in vivo and for future clinical applications.
|
