2011 Fiscal Year Final Research Report
Development of novel anticancer strategy by combining immunotherapy and surgery in gastrointestinal tumors
| Project/Area Number |
21591648
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | Nara Medical University |
|---|
Principal Investigator |
SHO Masayuki 奈良県立医科大学, 医学部, 准教授 (50364063)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Keywords | 外科総論 |
|---|
| Research Abstract |
Memory T cells are well known to be critically important for host defence in humans. Although they have been also suggested to play a significant role in tumor immunity, their clinical importance remains largely unknown. In this study, we tried to reveal the clinical significance of tumor-infiltrating CD45RO+memory T cells in several gastrointestinal malignancies. We performed immunohistochemistry on gastrointestinal cancer tissues including pancreatic, esophageal, and gastric cancer. Then we counted the cells stained positively for CD45RO+infiltrating into cancer tissue. As a result, CD45RO+hi patients had a significantly better postoperative prognosis than CD45RO+lo patients. Furthermore, the CD45RO status correlated with local immune activation. We found that tumor-infiltrating CD45RO+memory T cell has a significant independent prognostic value in human pancreatic cancer, and also our data suggested that adaptive immune response is functionally important in this fatal disease. Based
… More
on these clinical data, we extended our study to examine several novel strategies targeting T cell negative pathway including PD-1 and CTLA-4.In murine tumor models, anti-PD-1 and anti-CTLA-4 mAb had a significant antitumor effect on the prevention of liver metastasis and established tumors. Interestingly, the combination of PD-1 and CTLA-4 blockade displayed significant synergistic antitumor effect and resulted in complete inhibition in almost all mice. Further studies indicated that the combined treatment of PD-1/CTLA-4 blockade induced long-lasting and antigen-specific antitumor effect with resistance to tumor rechallenge. Furthermore, we also evaluated the importance of a recently identified T cell negative costimulator, B7-H3 expression. In human pancreatic cancer, B7-H3 expression was observed in almost all patients. Interestingly, anti-B7-H3 blocking mAb had also significant antitumor effect in vivo, similar to PD-1 and CTLA-4 blockade. A series of our studies provide new insights into targeting T cell negative pathway in tumor immunity and suggest that these promising strategies are potentially effective in human cancers. Less
|
-
[Journal Article] Prognostic importance of tumour-infiltrating memory T cells in oesophageal squamous cell carcinoma2012
Author(s)
Enomoto K, Sho M, Wakatsuki K, Takayama T, Matsumoto S, Nakamura S, Akahori T, Tanaka T, Migita K, Ito M, Nakajima Y
-
Journal Title
Clin Exp Immunol
Volume: 168(2)
Pages: 186-91
DOI
Peer Reviewed
-
-
-
-
-
-
-
-
