Inverse correlation between tumoral indoleamine 2,3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: its association with disease progression and survival.
OBJECTIVE
Tumor escape from host immune systems is a crucial mechanism for disease progression. We recently showed that the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) is a prognostic indicator for endometrial cancer. The purpose of the present study was to investigate the relationship between IDO expression and tumor-infiltrating lymphocytes (TIL) or natural killer (NK) cells and to clarify their prognostic effect in endometrial cancer.


METHODS
Immunohistochemical staining for IDO expression in endometrial cancer tissues (n = 65) was done. Tumor-infiltrating CD3+ and CD8+ lymphocytes, as well as CD57+ NK cells, were counted in serial tissue sections.


RESULTS
High IDO expression in tumor cells was found in 32 of 65 cases and was positively correlated with myometrial invasion, nodal metastasis, and lymph-vascular space involvement. We also found a significant correlation between high IDO expression and reduced numbers of CD3+, CD8+, and CD57+ cells infiltrating into both the tumor epithelium and stroma. Patients with high IDO expression, a low number of stromal CD3 (<60), low intraepithelial CD8 (<25), or low stromal CD8 (<40) had significantly impaired progression-free survival. On multivariate analysis, IDO expression and the number of stromal CD3+ TILs were independent prognostic factors for impaired progression-free survival.


CONCLUSIONS
Tumoral IDO expression correlated with a reduced number of TILs and NK cells in endometrial cancer, possibly contributing to disease progression and impaired clinical outcome. These findings suggest that targeting IDO to restore host antitumor immunity may be a therapeutic strategy for endometrial cancer.
Ino
Kazuhiko
K
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan. kazuino@med.nagoya-u.ac.jp
Yamamoto
Eiko
E
Shibata
Kiyosumi
K
Kajiyama
Hiroaki
H
Yoshida
Norio
N
Terauchi
Mikio
M
Nawa
Akihiro
A
Nagasaka
Tetsuro
T
Takikawa
Osamu
O
Kikkawa
Fumitaka
F
D000328:Adult; D000368:Aged; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000276:immunology* / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis*; D007694:Killer Cells, Natural / Q000502:physiology; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology*; D008875:Middle Aged; D015999:Multivariate Analysis
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase