2013 Fiscal Year Annual Research Report
制御性T細胞による腫瘍内CD8+T細胞の活性抑制に関する研究
| Project/Area Number |
12F02423
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| Research Institution | Osaka University |
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Principal Investigator |
坂口 志文 大阪大学, 免疫学フロンティア研究センター, 教授
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| Co-Investigator(Kenkyū-buntansha) |
ADEEGBE Olakunle 大阪大学, 免疫学フロンティア研究センター, 外国人特別研究員
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| Keywords | Cancer / Immunotherapy / CD8 / Drug / Dysfunction / Protein |
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| Research Abstract |
The main purpose of our study is to investigate how T regulatory cells may contribute to impaired function of anti-cancer (CD8) T cells. In the current year, we focused on two key issues.
1. Assessing the function of these CD8 T cells when high numbers of Tregs are present in the cancer environment. Under this condition, these cells indeed functioned poorly. Removing Tregs however improved their function. Also, these I cells which normally show a "tired" appearance regained a healthier appearance based on a number of proteins that are associated with T cell dysfunction. This finding revealed that the suppressive activities of Treg cells have key impact on how cancer-fighting T cells ultimately perform.
2. Therapy of cancer. We have used skin cancer model in mice to determine effective approach to treat cancer and stop its growth. From the above studies, we reasoned that removing Tregs should be an essential component of a treatment strategy. This, combined with blocking the activity of some proteins that act like "brakes" on T cells, preventing their full function was ultimately our approach. Mice in which skin cancer was established were treated with a combination of drugs that remove Tregs and/or those that block inhibitory proteins. We demonstrated that such combination approach is effective in stopping aggressive growth of the cancer.
Overall, our findings provide potential tools that could be employed in cancer treatment. It also highlights the important issue of multiple approach to eliminate cancer such as removing suppressive cells and improving the functional capability of T cells.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Significant progress was made over the past year on this project. Given the complexity of cancer biology, it is not feasible to address every aspect of immune response to cancer. However, our main focus has always been on the effector CD8 cells, Treg cells, and to a lesser extent, CD4 non-Treg cells. Two cancer models have been tested so far in this project - a skin cancer model and a gut cancer model, both in mice. Similar findings have been seen in both cases with respect to the contribution of Treg cells in limiting anti-cancer T cell immune response. As far as timeline, progress in either model was made in expected time frames. With this in mind, It is my opinion that my progress has been good so far and I hope to improve even more so that the project is taken to a very satisfactory end and completion.
We are currently rounding up the investigations dealing with treatment as discussed above. These experiments should provide a good point to put together our findings in the form of a publication shortly. Within the past year, we have also published a review in Frontiers in immunology on a topic that deals with Treg cells in cancer. This was well received by the immunology community.
Overall, no major delays have been experienced in this project and it is anticipated that the results of our investigation will be disseminated shortly. I have also presented some aspects of our findings at national and international immunology conferences and anticipate doing so again in an upcoming Japanese cancer immunology society meeting
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| Strategy for Future Research Activity |
As I near the completion of my JSPS assignment and proposed experimental plans, year 2014 would mostly be devoted to finishing the last pieces of experiments to answer some of the pending experiments that arose during the course of carrying out the project. This is essential as it demonstrates thoroughness in dealing with the topic of the project. In addition, a significant amount of time and effort will be devoted to writing a manuscript to introduce our investigations to a wider scientific audience
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Research Products
(1 results)
