Abstract
Among the subsets of tumor-infiltrating lymphocytes (TILs), activated cytotoxic T lymphocytes (granzyme B+) have an antitumor effect, while regulatory T lymphocytes [forkhead box P3 (Foxp3)+] suppress the antitumor immune response. The aim of the present study was to investigate the possible associations between TIL subsets and survival outcomes in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). From January 2000 to December 2008, 30 patients who underwent curative distal pancreatectomy without neoadjuvant chemoradiotherapy due to left-sided PDAC were enrolled in the present study. TIL subsets were enumerated by immunohistochemical staining for cluster of differentiation (CD)3, CD4, CD8, Foxp3 and granzyme B in the intra-tumoral areas of tissue blocks. Patients were divided into two groups according to the median value of the absolute counts and relative ratios of TIL subsets. In the univariate analysis, age, gender, tumor size, nodal stage, tumor differentiation and lymphovascular/perineural invasion were not significantly associated with survival outcome. However, low levels of preoperative cancer antigen (CA) 19-9 were associated with a longer overall survival (OS), although the association was not significant (37 vs. 18 months; P=0.061). A high level of granzyme B+ was associated with enhanced disease-free survival (DFS) (25 vs. 10 months; P=0.023), and a low Foxp3+/granzyme B+ ratio was associated with a favorable prognosis in terms of DFS (25 vs. 8 months; P=0.008) and OS (47 vs. 17 months; P=0.003). In the multivariate analysis, the ratio of Foxp3+/granzyme B+ was an independent prognostic factor for determining DFS [Exp(B), 3.060; 95% confidence interval (CI), 1.259-47.436; P=0.014] and OS [Exp(B), 3.580; 95% CI, 1.460-8.780; P=0.005]. Among the clinicopathological factors, low levels of CA 19-9 were significantly associated with a low Foxp3+/granzyme B+ ratio (P=0.016). The results of the present study suggested that a low Foxp3+/granzyme B+ ratio may be useful for predicting a good prognosis in surgically resected left-sided PDAC.
| Original language | English |
|---|---|
| Pages (from-to) | 4477-4484 |
| Number of pages | 8 |
| Journal | Oncology Letters |
| Volume | 12 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2016 Dec |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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Prognostic impact of the tumor-infiltrating regulatory T-cell (Foxp3+)/activated cytotoxic T lymphocyte (granzyme B+) ratio on resected left-sided pancreatic cancer. / Hwang, Ho Kyoung; Kim, Hyoung Il; Kim, Se Hoon; Choi, Junjeong; Kang, Chang Moo; Kim, Kyung Sik; Lee, Woo Jung.
In: Oncology Letters, Vol. 12, No. 6, 12.2016, p. 4477-4484.Research output: Contribution to journal › Article
TY - JOUR
T1 - Prognostic impact of the tumor-infiltrating regulatory T-cell (Foxp3+)/activated cytotoxic T lymphocyte (granzyme B+) ratio on resected left-sided pancreatic cancer
AU - Hwang, Ho Kyoung
AU - Kim, Hyoung Il
AU - Kim, Se Hoon
AU - Choi, Junjeong
AU - Kang, Chang Moo
AU - Kim, Kyung Sik
AU - Lee, Woo Jung
PY - 2016/12
Y1 - 2016/12
N2 - Among the subsets of tumor-infiltrating lymphocytes (TILs), activated cytotoxic T lymphocytes (granzyme B+) have an antitumor effect, while regulatory T lymphocytes [forkhead box P3 (Foxp3)+] suppress the antitumor immune response. The aim of the present study was to investigate the possible associations between TIL subsets and survival outcomes in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). From January 2000 to December 2008, 30 patients who underwent curative distal pancreatectomy without neoadjuvant chemoradiotherapy due to left-sided PDAC were enrolled in the present study. TIL subsets were enumerated by immunohistochemical staining for cluster of differentiation (CD)3, CD4, CD8, Foxp3 and granzyme B in the intra-tumoral areas of tissue blocks. Patients were divided into two groups according to the median value of the absolute counts and relative ratios of TIL subsets. In the univariate analysis, age, gender, tumor size, nodal stage, tumor differentiation and lymphovascular/perineural invasion were not significantly associated with survival outcome. However, low levels of preoperative cancer antigen (CA) 19-9 were associated with a longer overall survival (OS), although the association was not significant (37 vs. 18 months; P=0.061). A high level of granzyme B+ was associated with enhanced disease-free survival (DFS) (25 vs. 10 months; P=0.023), and a low Foxp3+/granzyme B+ ratio was associated with a favorable prognosis in terms of DFS (25 vs. 8 months; P=0.008) and OS (47 vs. 17 months; P=0.003). In the multivariate analysis, the ratio of Foxp3+/granzyme B+ was an independent prognostic factor for determining DFS [Exp(B), 3.060; 95% confidence interval (CI), 1.259-47.436; P=0.014] and OS [Exp(B), 3.580; 95% CI, 1.460-8.780; P=0.005]. Among the clinicopathological factors, low levels of CA 19-9 were significantly associated with a low Foxp3+/granzyme B+ ratio (P=0.016). The results of the present study suggested that a low Foxp3+/granzyme B+ ratio may be useful for predicting a good prognosis in surgically resected left-sided PDAC.
AB - Among the subsets of tumor-infiltrating lymphocytes (TILs), activated cytotoxic T lymphocytes (granzyme B+) have an antitumor effect, while regulatory T lymphocytes [forkhead box P3 (Foxp3)+] suppress the antitumor immune response. The aim of the present study was to investigate the possible associations between TIL subsets and survival outcomes in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). From January 2000 to December 2008, 30 patients who underwent curative distal pancreatectomy without neoadjuvant chemoradiotherapy due to left-sided PDAC were enrolled in the present study. TIL subsets were enumerated by immunohistochemical staining for cluster of differentiation (CD)3, CD4, CD8, Foxp3 and granzyme B in the intra-tumoral areas of tissue blocks. Patients were divided into two groups according to the median value of the absolute counts and relative ratios of TIL subsets. In the univariate analysis, age, gender, tumor size, nodal stage, tumor differentiation and lymphovascular/perineural invasion were not significantly associated with survival outcome. However, low levels of preoperative cancer antigen (CA) 19-9 were associated with a longer overall survival (OS), although the association was not significant (37 vs. 18 months; P=0.061). A high level of granzyme B+ was associated with enhanced disease-free survival (DFS) (25 vs. 10 months; P=0.023), and a low Foxp3+/granzyme B+ ratio was associated with a favorable prognosis in terms of DFS (25 vs. 8 months; P=0.008) and OS (47 vs. 17 months; P=0.003). In the multivariate analysis, the ratio of Foxp3+/granzyme B+ was an independent prognostic factor for determining DFS [Exp(B), 3.060; 95% confidence interval (CI), 1.259-47.436; P=0.014] and OS [Exp(B), 3.580; 95% CI, 1.460-8.780; P=0.005]. Among the clinicopathological factors, low levels of CA 19-9 were significantly associated with a low Foxp3+/granzyme B+ ratio (P=0.016). The results of the present study suggested that a low Foxp3+/granzyme B+ ratio may be useful for predicting a good prognosis in surgically resected left-sided PDAC.
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UR - http://www.scopus.com/inward/citedby.url?scp=84995783932&partnerID=8YFLogxK
U2 - 10.3892/ol.2016.5252
DO - 10.3892/ol.2016.5252
M3 - Article
AN - SCOPUS:84995783932
VL - 12
SP - 4477
EP - 4484
JO - Oncology Letters
JF - Oncology Letters
SN - 1792-1074
IS - 6
ER -