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Objective:To investigate the risk factors for lymph node metastasis in T1 colorectal cancer and application value of its nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 914 patients with T1 colorectal cancer who underwent radical resection in the Zhongshan Hospital of Fudan University from June 2008 to December 2019 were collected. There were 528 males and 386 females, aged from 25 to 87 years, with a median age of 63 years. Observation indicators: (1) clinicopathological data of patients with T1 colorectal cancer; (2) follow-up; (3) analysis of influencing factors for lymph node metastasis; (4) development and internal validation of a nomogram predition model. Patients were regularlly followed up once three months within postoperative 2 years and once six months thereafter to detect tumor recurrence and survival. The endpoint of follow-up was at postoperative 5 years. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the Logistic regression analysis. Based on results of multivariate analysis, a Logistic regressional nomogram for prediction of lymph node metastasis probability was constructed using R language software. The calibration curve was used to evaluate the consistency between probability predicted by the nomogram model and actual observation probability, which was reprensented by a consistency index. The Bootstrap method was used for evaluation of the model performance to receive the calibration curve. The Hosmer-Lemeshow test was used to calculate the goodness of fit in model. Results:(1) Clinicopathological data of patients with T1 colorectal cancer: 687 of 914 patients underwent direct surgery and 227 underwent remedial operation after endoscopic resection. All the 914 patients were confirmed as pT1NxM0 colorectal cancer by pathological examination. The tumor diameter was (2.3±1.2)cm. The pathological catogaries of 914 patients included 865 cases of adenocarcinoma and 49 cases of mucinous adenocarcinoma. The tumor differentiation degree of 914 patients included 727 cases of high or middle differentiation and 187 cases of low differentiation or undifferentiation. Of the 914 patients, 633 cases had submucosal infiltration depth ≥1 000 μm and 281 cases had submucosal infiltration depth <1 000 μm. There were 110 cases with nerve vessel invasion and 804 without nerve vessel invasion. The number of intraoperative lymph node dissection was 13 (range, 1-48). There were 804 cases in stage N0 of N staging, 98 cases in stage N1 and 12 cases in stage N2. There was no perioperative death. (2) Follow-up: 886 of 914 patients were followed up for 25 months (range, 1-129 months). During the follow-up, 24 patients had tumor recurrence or metastasis. The 5-year cumulative tumor recurrence rate of 914 patients was 4.8% and the median recurrence time was 17.0 months. Liver was the main site of tumor recurrence, accounting for 58.3%(14/24). The 5-year recurrence-free survival rate of 914 patients was 95.2%. The 5-year recurrence-free survival rate was 96.3% of 804 patients without lymph node metastasis, versus 86.6% of 110 patients with lymph node metastasis, showing a significant difference between the two groups ( χ2=6.83, P<0.05). (3) Analysis of influencing factors for lymph node metastasis: results of univariate analysis showed that preoperative carcinoembryonic antigen (CEA), preoperative CA19-9, tumor differentiation degree, submucosal infiltration depth, nerve vessel invasion were related factors for lymph node metastasis in T1 colorectal cancer ( odds ratio=2.56, 3.25, 2.21, 2.68, 3.39, 95% confidence interval as 1.41-4.67, 1.22-8.66, 1.43-3.41, 1.56-4.88, 2.10-5.48, P<0.05). Results of multivariate analysis showed that preoperative CEA ≥5 μg/L, preoperative CA19-9 ≥37 U/mL, poor differentiation or undifferentiation, submucosal infiltration depth ≥1 000 μm and nerve vessel invasion were independent risk factors for lymph node metastasis in T1 colorectal cancer ( odds ratio=2.23, 3.47, 2.01, 2.31, 2.91, 95% confidence interval as 1.02-4.15, 1.08-10.87, 1.03-3.27, 1.40-4.47, 1.64-5.13, P<0.05). (4) Development and internal validation of a nomogram predition model: based on results of multivariate Logistic analysis, a nomogram prediction model for lymph node metastasis in T1 colorectal cancer was developed. The nomogram score was 59 for preoperative CEA >5 μg/L, 100 for preoperative CA19-9 ≥37 U/mL, 48 for poor differentiation or undifferentiation, 67 for submucosal infiltration depth ≥1 000 μm and 92 for nerve vessel invasion, respectively. The total of different scores for different clinicopathological factors corresponded to the probability of lymph node metastasis. The receiver operating characteristic curve was drawed to evaluate the predictive performance of nomogram for lymph node metastasis in T1 colorectal cancer, with the area under curve of 0.70(95% confidence interval as 0.64-0.75, P<0.05). The Bootstrap internal validation of predictive performance in the nomogram predition model showed a consistency index of 0.70 (95% confidence interval as 0.65-0.75). The calibration chart showed a good consistency between the probability predicted by the nomogram model and actual probability of lymph node metastasis. The Hosmer-Lemeshow test showed a good fitting effect in model ( χ2=1.61, P>0.05). Conclusions:Preoperative CEA ≥5 μg/L, preoperative CA19-9 ≥37 U/mL, poor differentiation or undifferentiation, submucosal infiltration depth ≥ 1 000 μm and nerve vessel invasion are independent risk factors for lymph node metastasis in T1 colorectal cancer. The constructed nomogram model can help predict the probability of lymph node metastasis in T1 colorectal cancer.
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Natural killer T(NKT) cells are a heterogeneous group T cells that share properties of both natural killer cells and T cells,play an important role in tumor immunity.Related researches have confirmed that actived NKT cells can inhabit tumor progress,but activated NKT cells commonly become anergic for some unknown reasons after a short time.This article reviews researches on the possible mechanisms and solutions to NKT cells anergy.
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Objective To design a new cancer vaccine by using alpha-galactosylceramide (α-Galcer,α-GC) loaded tumor cells in combination with TLR 9 ligand and to evaluate its therapeutic effects on colon canc-er in mice.Methods MC38 cells were transfected with lentivirus (GFP-CD1d) to prepare CD1d-MC38 cells. The expression of CD1d molecules in CD1d-MC38 cells was detected by fluorescence microscopy , RT-PCR and flow cytometry.The sorted CD1d-MC38 cells were loaded with α-Galcer to prepare CD1d-MC38/α-GC complex. Flow cytometry was performed to evaluate the efficiency of combination .A mouse model of colon cancer was es-tablished to investigate the therapeutic effects of α-Galcer loaded tumor cells in combination with TLR 9 ligand ( CD1d-MC38/α-GC+CpG1826) on colon cancer in mice by analyzing tumor growth and mice survival time .Im-munohistochemical staining was used to detect CD 4+T and CD8+T infiltrating lymphocytes in tumor tissues .Re-sults The MC38 cancer cells that expressed CD 1d and GFP were successfully constructed , among which 98.10%±2.53%were positive for CD1d.Moreover, the CD1d-MC38 cells could combine with α-Galcer effec-tively in a dose and time dependent manner .Compared with PBS treated group ,α-GC treated group and TLR9 ligand treated group , the experimental vaccine strategy was sufficient to inhibit the growth of established tumors and prolong survival of tumor-bearing mice (P<0.01).Immunohistochemistry analysis revealed that levels of CD4+T cells and CD8+T cells in experiment group were significantly higher than those in groups treated with PBS,α-GC and TLR9 ligand (P<0.01).Conclusion CD1d-MC38/α-GC in combination with CpG1826 could efficiently inhibit the growth of established tumors and prolong survival of tumor-bearing mice .Immunohisto-chemistry analysis revealed that CD 4+T cells and CD8+T cells played important roles in anti-tumor immunity.
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Dendritic cells(DCs) are the most potent antigen presenting cells,which play a vital role in the initiation of immune response by presenting antigens to T cells and followed by induction of T-cell response.This established function of dendritic cells has attracted much attention in efforts to develop useful vaccines for the treatment of cancer.In several studies,DCs were genetically engineered by tumor-associated antigens or by immune molecules such as costimulatory molecules,cytokines,and chemokines.These new DC vaccines are more powerful in stimulating anti-tumor immunity.This review focuses on DC gene modifications for enhancing the multiple effector functions of DC,a variety of transferred genes,and recent clinical trials.