Expression and clinical significance of PD-L1 and infiltrated immune cells in the gastric adenocarcinoma microenvironment.

Programmed death-ligand 1 (PD-L1) is a crucial negative costimulatory molecule expressed on both tumor and immune cells. It binds to programmed death-1, facilitating tumor escape. Tumor-infiltrating immune cells play a vital role in this process. However, the clinical relationship between PD-L1 expression and tumor-infiltrating immune cells remains uncertain. Immunohistochemistry (IHC) was utilized to assess PD-L1 expression and TIIC markers (CD3, CD4, CD8, CD19, CD31, CD68, CD11c, CD56, and α-smooth muscle actin) in gastric adenocarcinoma tissues from 268 patients. The aim was to explore the prognostic significance of PD-L1 and the infiltration of different immune cell types. The study analyzed overall survival and the correlations between PD-L1 expression, immune cell infiltration, and clinicopathological characteristics. Among the 268 patients, 52 (19.40%) exhibited high PD-L1 expression on tumor cells (TPD-L1), while 167 (62.31%) displayed high PD-L1 expression on immune cells (IPD-L1). Patients with high IPD-L1 expression showed improved survival compared to those with low IPD-L1 expression (P = .028). High TPD-L1 expression associated with various clinicopathological features, such as larger tumor size, poorer differentiation, deeper invasion depth, and higher tumor stage. Conversely, patients with high IPD-L1 expression exhibited shallower tumor invasion and lower mortality rates. Univariate analysis indicated that superficial tumor infiltration, absence of lymph node and distant metastasis, low tumor stage, high IPD-L1 expression, and elevated CD8 and CD19 expression were associated with a reduced risk of tumor progression. Multivariate analysis revealed that patients with high IPD-L1 and CD8 expression or high TPD-L1 and low CD31 expression experienced significantly better overall survival than patients with other combinations. The findings indicate that patients with high PD-L1 expression in immune cells have a substantially improved prognosis. Additionally, the combination of PD-L1 with CD8 or CD31 expression status can serve as an indicator of prognosis in patients with gastric adenocarcinoma.

Long Noncoding RNA IPW Is a Novel Diagnostic and Predictive Biomarker in Lung Adenocarcinoma.

Background: Long non-coding RNAs (lncRNAs), as functional components of the human genome, are widely involved in cell proliferation, differentiation, apoptosis, migration and invasion by several types of cancer, including lung cancer. However, the role of lncRNA IPW in lung cancer has not been fully elucidated. The aim of the present study was to characterize the expression and clinical significance of lncRNA IPW in lung cancer. Materials and Methods: IPW expression in tumor samples and cells was assessed using the Oncomine and Cancer Cell Line Encyclopedia (CCLE) database, respectively. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine IPW expression and microRNA-370 (miR-370) expression. The clinical significance of IPW was evaluated by Chi-square test and Kaplan-Meier pot analyses. In addition, the sulforhodamine blue (SRB) assays was used to detect cell proliferation in IPW-overexpressed A549 cells. Results: IPW expression was significantly down-regulated in NSCLC tissues and was significantly associated with many clinicopathological data, including smoking history, differentiation, pT factor, pN factor and pTNM stage (p < 0.05). Decreased IPW expression was correlated with poor survival (p = 1.5e-05) and was positively associated with first progression in patients with lung adenocarcinoma (p = 0.00041). Furthermore, IPW could inhibit A549 cell proliferation and expression of miR-370. High miR-370 expression was associated with poor overall survival (OS) among lung adenocarcinoma patients (p = 0.045). Conclusions: These findings provide evidence that down-regulation of IPW might be considered as a beneficial prognostic biomarker and that it could potentially serve as therapeutic target in lung adenocarcinoma.

The performance and microbial communities of Anammox and Sulfide-dependent autotrophic denitrification coupling system based on the gel immobilization.

Anammox and sulfide-dependent autotrophic denitrification (ASDAD) coupling system can improve the nitrogen removal, but high sulfide concentration will affect the activity of anaerobic ammonia-oxidizing bacteria (AnAOB). Gel immobilization technology can enhance the survivability of microorganisms in unsuitable environments. Therefore, in this investigation, gel immobilization technology was applied into the ASDAD coupling system to explore the removal performance and microbial communities. The results showed that the optimal S2-/NO3- was 0.6, under which the best TN removal efficiency was 85.69%. The removal performance of ASDAD coupling system was stable under rapid variations of nitrogen loading rate and sulfide loading rate. Immobilized sludge cubes could attenuate the effects of temperature on AnAOB and sulfide-oxidizing bacteria. Observations of SEM and stereoscope suggested that AnAOB was more likely to exist on the surface of the sludge cubes. Thiobacillus, Candidatus Brocadia, and Candidatus Kuenenia were the main functional bacteria in the coupling system.

Overexpression of B7-H4 is associated with infiltrating immune cells and poor prognosis in metastatic colorectal cancer.

Metastasis commonly occurs in colorectal cancer (CRC) patients and confers a poor prognosis. B7-H4, an immune checkpoint molecule, has been found to be expressed in numerous tumor tissues and play critical roles in tumor progression. However, B7-H4 expression and its prognostic significance in different metastases from CRC remain unclear. In the present study, we screened a novel mouse anti-human B7-H4 monoclonal antibody (mAb) which exhibited a higher degree of recognition and sensitivity than the commercial reagent in immunohistochemistry (IHC). Using this antibody, overall 110 metastatic and paired primary lesions of CRC were analyzed for their expression of B7-H4, CD8 and CD68. Our results showed that expression of B7-H4 and CD68 in metastastic lesions was significantly higher than that in matched primary lesions (P = 0.0016, P < 0.0001). We also found a significant increase of CD68-positive immune cell infiltration in the B7-H4 high expressing metastases (P = 0.041). Moreover, upregulated B7-H4 in metastatic lesions was correlated with poor prognosis of patients (P = 0.014), while in primary lesions, B7-H4 combined with CD8 was associated with the overall survival (OS) (P = 0.043). Further, B7-H4 expression in metastatic lesions was significantly correlated with hazard ratio (HR) both in univariate and multivariate analysis. Altogether, B7-H4 in metastatic lesions is promising to be a potential prognostic indicator of CRC, and may promote tumor progression and metastasis of this cancer.

Effects of loading rates and N/S ratios in the sulfide-dependent autotrophic denitrification (SDAD) and Anammox coupling system.

This study investigated the shock resistance and the stability of a novel sulfide-dependent autotrophic denitrification (SDAD) and anaerobic ammonium oxidation (Anammox) coupling process for simultaneous removal of sulfide and nitrogen-containing wastewater in a single reactor. Results show that the total nitrogen (TN) removal efficiency reached 86.7% at a nitrogen loading rate (NLR) of 1.52 kgN m-3 d-1. Sulfide was fully oxidized, achieving the removal efficiency of 100% throughout the whole process. Batch tests suggest that Anammox remained dominant with the cooperation of partial SDAD (PSDAD) and could always compete over short-cut SDAD (SSDAD) for nitrite. High-throughput sequencing analysis revealed that Anammox bacteria remained active despite a relatively lower abundance and diversity than denitrifying bacteria. Candidatus Kuenenia might be the main contributor to Anammox, while Thiobacillus and Sulfurimonas were closely related to SDAD.

Association of increased B7 protein expression by infiltrating immune cells with progression of gastric carcinogenesis.

B7 negative costimulatory molecules are a group of molecules associated with the occurrence, development, and therapy of cancers. Here, we aimed to determine the clinical significance of PD-L1, B7-H3, and B7-H4 and their expression in CD8 and CD68 positive cells at different stages of gastric carcinogenesis.We detected PD-L1, B7-H3, B7-H4, CD8, and CD68 expression in samples by immunohistochemical staining of 62 chronic superficial gastritis (CSG) samples, 72 chronic atrophic gastritis (CAG) samples, 68 low-grade intraepithelial neoplasia (LIN) samples, 65 high-grade intraepithelial neoplasia (HIN) samples obtained from gastroscopic biopsies and 50 gastric adenocarcinoma (GA) samples obtained from surgical resections. Then we statistically analyzed the expression differences and correlations.Our results indicated that B7 and CD68 expression on infiltrating immune cells was associated with disease progression. However, infiltration of CD8+ cells decreased with disease progression. B7-H3 expression was markedly enhanced at neoplasia and GA stages. B7-H3 in tumor cells was negatively correlated with CD8-expressing cells. Conversely, B7-H3 expression in tumor-infiltrating immune cells was positively correlated with CD68-expressing cells. B7-H4 expression was found in the cell membrane at the stages of gastritis and low-grade neoplasia and was gradually expressed in the cytoplasm at high-grade neoplasia and GA stages. High B7-H4 expression in infiltrating immune cells was also significantly associated with lower CD8-positive and higher CD68-positive cell densities.Increased B7 protein expression by infiltrating immune cells was associated with disease progression, and specifically, the level of B7-H3 expression and localization of B7-H4 expression differed significantly among different stages of gastric carcinogenesis.

Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas.

Background: B7-H3 promotes tumor immune escape and is highly expressed in tumor tissues. Stromal cells in tumors, including fibroblasts, play an important role in this process; however, the role of B7-H3 in tumor fibroblasts has not been fully clarified. Methods: We examined B7-H3, CD31, and alpha-smooth muscle actin (α-SMA) protein expression in 268 gastric adenocarcinomas (GACs) by immunohistochemistry. The coexpression of B7-H3 with CD31 or α-SMA was examined using immunofluorescence double staining. Cytokine expression from fibroblasts treated with B7-H3 small interfering RNA (siRNA) was analyzed by a Quantitative reverse transcription-polymerase chain reaction (qPCR) and Enzyme-linked immunosorbent assay (ELISA). The transwell tests were conducted to assess the migration and invasion ability of fibroblasts. The overall survival was analyzed by a Kaplan-Meier analysis. Associations between categorical variables were assessed using the Pearson's Chi-square test or Fisher's exact test. Results: GAC patients with B7-H3 expression showed significantly poorer survival (P = 0.012). The overall survival of the group with high B7-H3 expression was significantly worse than the group with low B7-H3 expression in both tumor cells and in stromal cells (P = 0.007 and P = 0.048, respectively). B7-H3 expression correlated with many clinicopathological data, including tumor stage, tumor depth, lymph node involvement, and survival. Immunofluorescence staining showed that B7-H3 was expressed in tumor cells and α-SMA-positive fibroblasts. Remarkably, high expression of α-SMA was associated with a poor prognosis (P = 0.007), and the prognoses of patients with high stromal expression of B7-H3 and α-SMA were significantly worse than that of other combination types (P = 0.001). Additionally, the absence of B7-H3 led to decreased secretion of cytokines, such as interleukin (IL)-6 and vascular endothelial growth factor (VEGF), as well as a decline in migration and invasion ability in cancer-associated fibroblasts (CAFs). Conclusions: Patients with high B7-H3 expression either in tumor cells or in stromal cells had significantly poorer overall survival. Stromal B7-H3 expression was mostly detected in α-SMA-positive CAFs. GAC patients with both stromal B7-H3-high and α-SMA-high expression had significantly poorer overall survival, suggesting that stromal B7-H3 and α-SMA expression status can serve as an indicator of poor prognosis for GAC patients.