XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Clinical significance of IFIT2 expression in human renal cancer tissues.

BACKGROUND: Interferon (IFN)-induced protein with tetratricopeptide repeats 2 (IFIT2) is an important member of the IFN-stimulated gene (ISG) family. It has been demonstrated that IFIT2 is important in the physiopathological processes of antiviral and antitumor activities. We previously demonstrated that IFIT2 was highly expressed in paracarcinoma tissues compared with gastric cancer tissues, and its expression level was positively correlated with a superior postoperative prognosis of the patients. METHODS: We performed immunohistochemical staining of IFIT2 in human clear cell renal cell carcinoma (ccRCC) tissues by using a tissue microarray. RNAseq data of kidney clear cell carcinoma (KIRC) samples from The Cancer Genome Atlas (TCGA) were used to perform the enrichment analyses based on the genes that were highly correlated with IFIT2. RESULTS: Weak staining of IFIT2 was located on the cytoplasm and cell membrane surface of the cancer cells, while positive staining of IFIT2 was located mainly on adjacent normal tissues. Survival analysis showed that patients with higher IFIT2 expression had better overall survival than patients with lower IFIT2 expression (P=0.030). The Cox model further demonstrated that age (P=0.002), pathological stage (P=0.000), TNM stage (P=0.005) and IFIT2 expression (P=0.003) could be used as independent prognostic predictors for ccRCC patients. Additionally, the enrichment analysis based on ccRCC expression profile data extracted from TCGA revealed that the genes highly correlated with IFIT2 were mainly related to the biological processes of virus response, T cells and the innate immune response (GO:0009615, GO:0042110, and GO:0045088) and the pathways of NLR signaling, chemokine signaling, and TLR signaling (hsa04621, hsa04062, and hsa04620). CONCLUSIONS: IFIT2 could serve as a potential prognostic marker for ccRCC patients, and the mechanism of decreased IFIT2 expression in the progression of ccRCC merits further investigation.

microRNA-181b suppresses the metastasis of lung cancer cells by targeting sex determining region Y-related high mobility group-box 6 (Sox6).

BACKGROUND: The aim of the study was to measure the expression of microRNA (miR)-181b in patients with lung cancer, investigate its biological function and elucidate the underlying mechanisms associated with the development of lung cancer. METHODS: miR-181b expression in tissues was measured via RT-qPCR. After A549 cells were transfected with miR-181b mimic or si-Sox6, the proliferation, migration and cell cycle distribution of A549 were evaluated using cell counting kit-8 assay, transwell assay and flow cytometry. The levels of cell cycle-related proteins and Sox6 were analyzed by western blotting. Gene targets of miR-181b were predicted via bioinformatics analysis and verified using a dual-luciferase reporter gene assay. RESULTS: Expression of miR-181b was significantly downregulated in lung cancer tissues (P < 0.05), and was inversely correlated with the degree of cell differentiation and clinical stages of lung cancer (both P < 0.05). Additionally, the expression of miR-181b was significantly lower in adenocarcinoma compared with squamous cell carcinoma in the lungs (P < 0.05). Overexpression of miR-181b significantly decreased the protein level of Sox6 and significantly suppressed the cell proliferation and metastasis (both P < 0.05); this effect was also observed in A549 cells transfected with si-Sox6. The luciferase activity of a Sox6 3'-untranslated region-based reporter construct was significantly lower when transfected with miR-181b (P < 0.05), which suggests that Sox6 is a direct target of miR-181b. CONCLUSION: The results of the present study suggest that miR-181b may function as a tumor inhibitor in the development of lung cancer via targeting Sox6 to decrease the proliferation and metastasis of lung cancer cells.

[Removal of AOX, Chroma and TOC in Chemical Dyestuff Wastewater with Iron Scraps-Fenton-Coagulation Combined Process].

Iron scraps-Fenton-coagulation process was applied to chemical dyestuff wastewater. The removal performance of absorbable organic halogens(AOX), chroma and total organic carbon (TOC) was investigated at different molar ratios of Fe2+ to H2O2 (1:3-1:15), iron scraps reaction time (2-5 h) and Fenton reaction time (20-80 min). The results showed that the removal ratios of AOX, chroma and TOC firstly increased and then decreased with the decrease of the molar ratio of Fe2+ to H2O2, while continuously increased with the increase of iron scraps and Fenton reaction time. The optimal condition was determined as Fe2+:H2O2 ratio of 1:8, iron scraps reaction time of 4 h and Fenton reaction time of 60 min, under which 94.2% of AOX, 93.7% of chroma and 27.2% of TOC were removed. A comparison study revealed that the iron scraps-Fenton-coagulation combined process could achieve much better removal of AOX, chroma and TOC than any other single or combined processes of iron treatment, Fenton oxidation and coagulation. GC-MS analysis revealed that halogenated compounds and anilines were efficiently removed, as well as nitrobenzenes, phenols, benzaldehydes, ethers, nitriles and heterocyclic compounds.·OH was found to devote much in the Fenton reaction according to the tert-butyl alcohol trapping hydroxyl radicals test.

High expression of CD11c indicates favorable prognosis in patients with gastric cancer.

AIM: To determine the relationship between CD11c expression level and prognosis in patients with gastric cancer (GC). METHODS: This retrospective survival study was performed from July 31, 2008 to June 30, 2014. Our study inclusion criteria included all the patients with GC who underwent surgical resection between January 1998 and December 2009 in the Third Affiliated Hospital of Soochow University. CD11c expression levels in 140 patients with GC at different UICC stages were evaluated using immunohistochemistry, and GC tissues from 16 cases were further verified by qRT-PCR. The χ (2) test was used to compare the patient- and disease-related factors between the low CD11c expression group and the high expression group. Univariate probabilities of overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. The log rank test was used to compare survival curves. Different multivariate COX models were used to estimate the association between CD11c expression and both death and recurrence risk in GC patients. RESULTS: The average CD11c expression level was 5.1 ± 1.8/high power field (HPF) in 10 gastritis samples, 4.5 ± 2.3/HPF in 10 gastric polyp samples and 9.7 ± 6.3/HPF in 140 gastric cancer samples, respectively. The CD11c expression level was significantly decreased from UICC stage I to stage IV (stage I: 16.0 ± 7.4, stage II: 10.4 ± 5.5, stage III: 9.4 ± 6.1, stage IV: 5.3 ± 3.2, P < 0.001). Patients in the high CD11c expression group had a greater 3- and 5-year OS probability and longer median survival time compared with the low CD11c expression group, (67.7% vs 39.2%; 51.4% vs 29.0%; 67.0 mo vs 28.0 mo; χ(2) = 6.80, P = 0.009), and had a greater 3- and 5-year DFS probability and longer median DFS time (63.7% vs 24.0%; 49.1% vs 11.9%; 64.0 mo vs 18.0 mo; χ (2) = 15.39, P < 0.001). Patients with high CD11c high expression had a reduced risk of death (HR = 0.56, 95%CI: 0.33-0.98, P < 0.05) and relapse (HR = 0.39, 95%CI: 0.23-0.67, P < 0.01) compared with patients with low CD11c expression after adjustment of potential confounders, with the exception of tumor size. However, the protective effect related to death (HR = 0.90, 95%CI: 0.49-1.67, P = 0.749) and relapse (HR = 0.65, 95%CI: 0.36-1.19, P = 0.160) disappeared when tumor size was incorporated into the model. CONCLUSION: High expression of CD11c decreased the risk of death and relapse, and may be regarded as an alternative indicator of favorable prognosis in patients with GC.

The status of perineural invasion predicts the outcomes of postoperative radiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT). PATIENTS AND METHODS: We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients' outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI. RESULTS: Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn't improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05). CONCLUSIONS: PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results.

Proposed Modification of Nodal Staging as an Alternative to the Seventh Edition of the American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Improves the Prognostic Prediction in the Resected Esophageal Squamous-Cell Carcinoma.

INTRODUCTION: The 7th American Joint Committee on Cancer (AJCC) tumor-node-metastasis staging system for esophageal cancer defined N classification based on the number of metastatic lymph nodes (LNs). However, this classification might neglect the extent of LNs metastasis. This study aimed to revise N classification based on the extent of LNs metastasis and propose a modification to the current AJCC staging system for better representing the prognostic characteristics of Chinese esophageal squamous-cell carcinoma (ESCC). METHODS: We retrospectively reviewed 1993 ESCC patients who underwent curative resection. The proposed N categories based on the number of LNs metastasis stations were compared with the current staging system by univariate and multivariate Cox regression analyses. Homogeneity, discriminatory ability, and monotonicity of gradients of two staging systems were compared using likelihood ratio χ statistics and Akaike information criterion calculations. RESULTS: The survival differences were not significant for N2 versus N3 category (p = 0.231) and stages IIIB versus IIIC (p = 0.713) based on the 7th AJCC staging system. When the modified staging system was adopted, the survival difference for N2 versus N3 and IIIB versus IIIC could be well discriminated. Statistical analysis showed that the modified staging system had higher likelihood ratio χ scores and smaller Akaike information criterion values than the 7th AJCC staging system, which represented the optimum prognostic stratification. CONCLUSIONS: The modified staging system with the revised N categories based on the number of LNs metastasis stations better predicts the survival of Chinese ESCC population than the 7th AJCC staging system. Further studies are required to confirm this result.

Ketamine attenuates the lipopolysaccharide-induced inflammatory response in cultured N2a cells.

The use of ketamine is recommended in patients with sepsis undergoing surgery due to its anti-inflammatory effects. However, a paucity of data exists with regard to the anti-inflammatory effects of ketamine in the central nervous system. Therefore, the present study aimed to investigate the effect of ketamine on lipopolysaccharide (LPS)­induced inflammatory responses in cultured Neuro2a (N2a) cells and to elucidate its potential mechanism of action. N2a cells were randomly divided into the following 3 groups (n=6): The DMEM culture solution administration alone group, the 0.5 µmol/l LPS administration alone group and the 1 µmol/l ketamine plus 0.5 µmol/l LPS administration group. The expression levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB and inducible nitric oxide synthase (iNOS) were determined. LPS-treated N2a cells exhibited a significant increase in the expression levels of IL-1ß, IL-6, TNF-α, NF-κB and iNOS, while the administration of ketamine eliminated the LPS-induced production of IL-1ß, IL-6, TNF-α, NF-κB and iNOS. Based on our data, we hypothesized that the anti-inflammatory effect exerted by ketamine on N2a cells was potentially due to the inhibition of NF-κB and iNOS.

Higher numbers of T-bet(+) intratumoral lymphoid cells correlate with better survival in gastric cancer.

In the present study, we studied the expression of T-bet, a key marker for type 1 immune responses, within the tumor microenvironment of gastric cancer, and analyzed its association with clinicopathological parameters. One hundred and fifty-two archival paraffin-embedded gastric tumor tissues were collected, and the expression of T-bet in these cancer tissue specimens was examined by immunohistochemistry. T-bet(+) tumor-infiltrating lymphocytes (TILs) in some gastric cancer tissues were further characterized by flow cytometric analysis. The density of T-bet(+) TILs in gastric cancer tissues in relation to patient's clinicopathological parameters and postoperative prognosis has been analyzed. Herein, we have found significant increases in T-bet(+) lymphocytes in tumor tissues as compared with normal stomach tissues, gastritis tissues or gastric polyp specimens. T-bet(+) cells mainly consisted of CD4(+), CD8(+) and CD56(+) TILs. In addition, lower numbers of T-bet(+) TILs were associated with poor clinicopathological parameters such as invasion to muscular layer, larger tumor size and advanced cancer stages. Moreover, patients with higher numbers of T-bet(+) TILs have longer disease-free survival and overall survival. Thus, our study supports the idea that tumor growth elicits spontaneous type 1 cellular immune responses and tumor progression is associated with suppression of antitumor immunity. T-bet expression within tumor can serve as a prognostic indicator for gastric cancer and a potential biomarker for immunotherapy.

[Apolipoprotein M expression in human colorectal cancer tissues and its clinicopathological relevance].

OBJECTIVE: To investigate the mRNA and protein expression levels of apolipoprotein M (apoM) in the human colorectal cancer tissues, and to explore its clinical relevance. METHODS: Real-time PCR was carried out to determine the mRNA expression levels both in cancer tissue and its adjacent normal tissue from 20 patients with colorectal cancer. Immunohistochemistry was also carried out to determine the protein levels in 23 colorectal biopsy samples (7 normal mucosa, 6 inflammatory mucosa and 10 polyp tissues) and 20 cases of colorectal cancer tissues as well as the adjacent normal tissues. RESULTS: Real-time PCR result showed that apoM mRNA level in the colorectal cancer tissues was significantly lower than that in their adjacent normal tissues (0.05±0.01 vs. 0.19±0.05, P<0.05). ApoM mRNA level in colorectal cancer tissues was statistically significant higher in the patients with lymph node metastasis as compared to the patients without lymph node metastasis (P<0.01). The median value of apoM protein in cancer tissues was 5.50, which was significantly lower than that in the adjacent normal tissues (10.5, P<0.05), inflammatory mucosa tissues (9.75, P<0.05), polyp tissues (11.0, P<0.01) and normal mucosa (10.5, P<0.05). No significant association was observed between the apoM protein level and the clinicopathological parameters of patients. CONCLUSIONS: Both apoM mRNA and protein expression levels in colorectal cancer tissues are significantly decreased in contrast to normal and benign colorectal tissues. The apoM mRNA expression in colorectal cancer tissues is closely associated with nodal metastasis.

B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma.

AIM: To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment. METHODS: One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study. Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues. Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow cytometry and immunofluorescence staining were used for detection of regulatory T cells. Data was analyzed with statistical software. RESULTS: Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues, localized in tumor cell membrane and cytoplasm, while weak or none expression of B7-H1 was detected in pared normal colorectal tissues. Meanwhile, CD3 positive T cells were found congregated in CRC tumor nest and stroma. Statistic analysis showed that B7-H1 expression level was negatively correlated to the total T cell density in tumor nest (P < 0.0001) and tumor stroma (P = 0.0200) of 102 cases of CRC tissues. Among the total T cells, a variable amount of regulatory T cells with a clear Foxp3⁺ (forkhead box P3) staining could be detected in CRC tissues and patients' blood. Interestingly, in the 33 samples (15 cases of B7-H1(high) CRC tissues and 18 cases of B7-H1(low) CRC tissues) of freshly isolated mononuclear cells from CRC tissues, the percentages of CD4⁺Foxp3⁺ and CD8⁺Foxp3⁺ regulatory T cells were found remarkably higher in B7-H1(high) CRC tissues than in B7-H1(low) CRC tissues (P = 0.0024, P = 0.0182), indicating that B7-H1 expression was involved in proliferation of regulatory T cell. No significant difference was found in CRC peripheral blood (P = 0.0863, P = 0.0678). PD-1 is the specific ligand for B7-H1 pathway transferring inhibitory signal to T cell, which is expressed by activated T cell. Our further analysis of PD-1 expression on T cells in CRC tissues showed that conventional T cells (CD4⁺Foxp3⁻/CD8⁺Foxp3⁻), which was thought to contribute to the anti-tumor immune response, highly expressed PD-1; while regulatory T cells (CD4⁺Foxp3⁺/CD8⁺Foxp3⁻) almost failed to express PD-1. The average percentage of PD-1 expression on regulatory T cells was significantly higher than the percentage of PD-1 on conventional T cells (CD4⁺Foxp3⁻ T cell, P < 0.0001; CD8⁺Foxp3⁻ T cell, P < 0.0001). The diverse expression of PD-1 might lead to different fate of T cell subsets in B7-H1 over-expression CRC tumor microenvironment. CONCLUSION: B7-H1 expression in tumor cells can inhibit the conventional T cell proliferation in tumor microenvironment through the PD-1 expression on conventional T cells.

B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma.

A retrospective cohort study including 112 patients suffering from esophageal squamous cell carcinoma (ESCC) was performed to investigate the expression of B7-H4 in ESCC and determine its association with patient's clinicopathological parameters and survival. Expression levels of B7-H4 on tumor cells and densities of tumor infiltrating lymphocytes (TILs) in the surgical specimens of ESCC tissues were characterized using immunohistochemical assays. Uni- and multivariate analyses were performed to evaluate the prognostic value of B7-H4 expression levels and densities of TILs in tumor sections. Positive B7-H4 immunostaining was observed in 107 of 112 (95.5%) of ESCC tissue sections. We further divided all patients into two major subgroups, a lower B7-H4 expression group with 46 patients and a higher B7-H4 expression group with 66 patients. We found that expression levels of B7-H4 on tumor cells were significantly correlated with patient's gender (P = 0.0288), distant metastasis (P = 0.0500), and TNM stage (P = 0.0258). Moreover, tumor cell B7-H4 expression was inversely correlated with densities of CD3(+) T cells in tumor nest (P = 0.0424) and CD8(+) T cells in tumor stroma (P = 0.0229). The overall survival rate of the patients with higher B7-H4 expression was significantly worse than that of the patients with lower B7-H4 expression (P = 0.0105, Hazard Ratio: 1.854, 95%CI:1.152-2.902). Markers of cell-mediated immune responses such as CD3, CD8, and T-bet were associated with better patient survival. The present study demonstrated that B7-H4 expression in human ESCC is associated with cancer progression, reduced tumor immunosurveillance and worse patient outcomes. B7-H4 can serve as a novel prognostic predictor for human ESCC and a potential target for the immune therapy against this malignancy.

Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients.

AIM: to analyze the correlation between cytokine-induced killer (cik) cells adoptive immunotherapy and cancer-related death in gastric cancer patients. methods: One hundred and fifty-six gastric cancer patients after operation at the Third Affiliated Hospital of Soochow University were enrolled in this study. Their clinical data including demographic characteristics, operation time, tumor size, pathological type and staging, tumor metastasis, outcome of chemotherapy or CIK cells adoptive immunotherapy, survival time or time of death were collected with a standard structured questionnaire. Kaplan-Meier method was used to estimate the median survival time, and the 2- and 5- year survival rates. Hazard risk (HR) and 95% confidence interval (95% CI) of CIK cells adoptive immunotherapy for gastric cancer were calculated using the two-stage time-dependent covariates Cox model. RESULTS: the survival time of gastric cancer patients was longer after CIK cells adoptive immunotherapy than after chemotherapy (χ(2) = 10.907, P = 0.001). The median survival time of gastric cancer patients was also longer after CIK cells adoptive immunotherapy than after chemotherapy (49 mo vs 27 mo, P < 0.05). The 2- and 5-year survival rates of gastric cancer patients were significantly higher after CIK cells adoptive immunotherapy than after chemotherapy (73.5% vs 52.6%, 40.4% vs 23.9%, P < 0.05). A significant difference was observed in the survival curve for patients who received CIK cells adoptive immunotherapy (0, 1-10, 11-25, and over 25 frequencies) (χ(2) = 14.534, P = 0.002). The frequencies of CIK cells adoptive immunotherapy were significantly related with the decreasing risk of death in gastric cancer patients after adjustment for sex and age of the patients, tumor stage and relapse (HR = 0.54, 95% CI: 0.36-0.80) when the first stage Cox model was used to define the subjects who remained alive beyond 36 mo as survivors. However, no correlation was observed between the frequencies of death in CIK cells adoptive immunotherapy and the risk of gastric cancer patients (HR = 1.09, 95% CI: 0.63-0.89) when the second stage Cox model was used to define the subjects who survived for more than 36 mo as survivors. CONCLUSION: the survival time of the gastric cancer patients treated with chemotherapy combined with CIK cells adoptive immunotherapy is significantly longer than that of the patients treated with chemotherapy alone and increasing the frequency of CIK cells adoptive immunotherapy seems to benefit patients more.

[Influence of co-stimulatory molecules B7-H4 expression on the prognosis of patients with gastric cancer treated with cytokine-induced killer cells adoptive immunotherapy].

OBJECTIVE: To investigate the influence of co-stimulatory molecules B7-H4 expression on prognosis of gastric cancer patients treated by cytokine-induced killer cells (CIK cells) adoptive immunotherapy. METHODS: Clinical data of 156 cases of gastric cancer patients were retrospectively analyzed. Patients were divided into chemotherapy group(n=81) and chemotherapy combined with CIK cell therapy group(n=75). B7-H4 expression was detected in the surgical specimens of gastric cancer patients by immunohistochemistry assay. Disease-free survival was compared between the chemotherapy group and the CIK group at different expression levels of B7-H4. RESULTS: The difference was not statistically significant in all clinical and pathological data between the chemotherapy group and the CIK treatment group (P>0.05). The postoperative median tumor-free survival in two groups was 18.0 and 45.0 months, respectively, and the difference was statistically significant (chi(2)=11.631, P=0.001). The postoperative median survival time was 27.0 and 49.0 months, respectively, and the difference was statistically significant (chi(2)=10.907, P=0.001). In 86 patients with low B7-H4 expression, the median tumor-free survival time was 32.0 and 62.0 months, respectively, and the difference was statistically significant (chi(2)=4.663,P=0.03). In 70 patients with high B7-H4 expression, the median tumor-free survival time was 11.0 and 18.0 months, respectively, and the difference was statistically significant (chi(2)=11.971, P=0.001). CONCLUSION: The median tumor-free survival time of patients with gastric cancer may be further improved by chemotherapy combined with CIK cell therapy, regardless of the level of B7-H4 expression.

Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma.

B7-H3, a member of the B7-family molecules, plays an important role in adaptive immune responses, and was shown to either promote or inhibit T-cell responses in various experimental systems. B7-H3 was expressed in some human cancers and correlated with poor outcome of cancer patients. However, its exact role in cancer is not known. In the present study, we studied the expression of B7-H3 in the pathologic specimens of 102 patients treated for colorectal carcinoma (CRC) by immunohistochemistry. Strong B7-H3 expression was found in cancer tissues from 54.3% CRC patients, while minimal expression was found in adjacent normal colorectal tissues. Higher B7-H3 expression in tumor positively correlated with a more advanced tumor grade. In addition, consistent with a role of B7-H3 in suppressing tumor immune surveillance, the expression of B7-H3 in cancer cells negatively correlated with the intensity of tumor infiltrating T lymphocytes in both tumor nest and tumor stroma. Furthermore, we found that the level of soluble B7-H3 in sera from CRC patients was higher than healthy donors. TNF-alpha, an important cancer-promoting inflammatory molecule, was subsequently found to significantly increase the release of soluble B7-H3 in colon cancer cell lines. Therefore, our data suggest that both soluble and membranous B7-H3 proteins are involved in colon cancer progression and evasion of cancer immune surveillance.