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Objective To understand the current status of research on lung cancer immunotherapy to provide a reference for further investigation and future topic selection in this field. Methods CiteSpace visualization analysis software was used to analyze 400 Chinese studies in CNKI and 5 001 English studies in the Web of Science database from 2005 to 2021, with "lung cancer" and "immunotherapy" as keywords. Keyword co-occurrence analysis was performed on 17 English studies of "Lung Cancer" "Immunotherapy" and "Single cell sequencing" in the Web of Science database. Results "Non-small cell lung cancer" "immunosuppressants" "PD-L1" "dendritic cells" and "cytokine-induced killer cells" are current research hotspots in lung cancer immunotherapy. Monoclonal antibody drugs including nivolumab, pembrolizumab, atezolizumab, and durvalumab are hotspot drugs. Immunotherapy combined with chemotherapy as well as PD-L1 expression have become the focus of continuous research. The majority of studies on lung cancer immunotherapy are conducted in the United States, followed by China. Conclusion Lung cancer immunotherapy has gradually become a research hot spot in China. In the future, in-depth research is needed to provide cutting-edge directions for lung cancer immunotherapy.

Immune checkpoint therapy is an emerging frontier in cancer therapy. With the aim to develop an efficient herb derived compound to facilitate immune checkpoint therapy, here we investigate if a herb‐derived compound, Bakuchiol (BAK), can be used to treat lung cancer and elucidate if BAK could serve as a PD‐L1 regulator. To this end, a murine lung cancer model was established by subcutaneously inoculating murine Lewis lung carcinoma (LLC) cells. BAK of 5 to 40 mg/kg was used for treatment in vivo for 15 days. On Day 15, the population of CD4+ and CD8+ T cells, Treg cells. BAK could effectively inhibit tumor growth by starting treatment either on Day 0 or 6 after tumor inoculation at doses of 5−40 mg/kg. BAK treatment increased the population of cytotoxic immune cells (i.e., CD8+ T cells, and M1 macrophages), meanwhile decreasing pro‐tumor immune cells (i.e., CD3+ T cells, Treg cells, and M2 macrophages). Anti‐inflammatory cytokines, including IL1β, IL2, IFNγ, TNF‐α, IL4 and IL10 were upregulated by BAK. PD‐L1 expression in the tumor was also lowered by BAK. AKT and STAT3 signaling were inhibited by BAK. BAK is an efficient agent in reducing LLC tumor growth. These data support the potential of BAK as a new drug for treating lung cancer by serving as a PD‐L1 inhibitor that suppresses the activation of AKT and STAT3. [ABSTRACT FROM AUTHOR]

Colon cancer poses a great threat to human health. Currently, there is no effective treatment for colon cancer due to its complex causative factors. Immunotherapy has now become a new method for tumor treatment. In this study, 487 DEGs were screened from The Cancer Genome Atlas (TCGA) database and ImmPort database, and GeneOntology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed. Hierarchical clustering of all samples revealed a significant correlation between colon cancer and immunity. The weighted gene co-expression network analysis (WGCNA) algorithm was used to identify key gene modules associated with immunity in colon cancer, here, module grey60 showed the highest correlation. A protein-protein interaction (PPI) network was constructed using the STRING database to screen hub genes, and subsequently, 7 immune-related genes the most closely associated with colon cancer were identified by differential expression in cancer and paracancer. Finally, a risk prediction model was developed using least absolute shrinkage and selection operator (LASSO) COX analysis, and the accuracy of the model was validated by GSE14333. This study determined that IRF4 and TNFRSF17 were immune-related genes in colon cancer, providing immune-related prognostic biomarkers for colon cancer. [ABSTRACT FROM AUTHOR]

Aberrant expression of long noncoding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) has been detected in human colorectal cancer (CRC). This study aimed to investigate the role of CDKN2B-AS1 and the underlying mechanism in human CRC. Gain- and loss-of-function assays were performed to explore the role of CDKN2B-AS1 in the malignant behavior of HCT116 and SW480 CRC cells in vitro and in vivo. RNA pull-down assay was conducted to identify the target of CDKN2B-AS1 in CRC cells. The physical and functional interactions between CDKN2B-AS1 and the target were examined. CDKN2B-AS1 inhibited CRC cell proliferation and migration while promoting apoptosis in vitro via activation of mitogen-activated protein kinase kinases (MEK)/extracellular signal-regulated kinase (ERK)/p38 signaling. CDKN2B-AS1 bound to mitogen-activated protein kinase (MAPK) inactivator dual-specificity phosphatase 1 (DUSP1) in CRC cells. In contrast to CDKN2B-AS1, DUSP1 promoted CRC cell proliferation, suppressed apoptosis and inactivated MEK/ERK/p38 signaling in CRC cells. Furthermore, CDKN2B-AS1 overexpression attenuated DUSP1 expression in normal colonic myofibroblasts and CRC cells. Overexpression of DUSP1 effectively countered the activation of MEK/ERK/p38 signaling induced by CDKN2B-AS1 overexpression or further blocked MEK/ERK/p38 signaling suppressed by CDKN2B-AS1 silencing. In the mouse xenograft model, CDKN2B-AS1 suppressed CRC growth, whereas DUSP1 promoted CRC growth. CDKN2B-AS1 induced cell apoptosis while suppressing EMT (epithelial–mesenchymal transition), whereas DUSP1 suppressed cell apoptosis while inducing EMT in CRC, as evidenced by the alterations in the protein levels of apoptosis and EMT markers in tumor tissue samples. CDKN2B-AS1 regulates CRC cell growth and survival by targeting MAPK inactivator DUSP1. [ABSTRACT FROM AUTHOR]

Background Manganese (Mn2+) has been shown to promote type I interferon (IFN) production and activate the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) signaling pathway, suggesting that Mn2+ could be used as an adjuvant for vaccination. Methods In present study, the effects of Mn2+ on vaccination against hepatitis B virus (HBV) were evaluated. We treated mouse hepatocytes and kuppfer cells with Mn2+ with or without adeno-associated virus (AAV)–HBV infection. Expression of IFN-α and IFN-β and activation of TBK1 and IRF3 were monitored. Wild-type and STING-/- mice were treated with Mn2+ and then infected with AAV-HBV. Serum levels of HBV surface antigen (HBsAg), alanine aminotransferase (ALT) activity, IFN-α, and IFN-β were detected. Lymphocyte infiltration in the liver was evaluated. HBsAg-Tg mice were vaccinated with Mn2+ and HBsAg. The serum levels of HBsAg antibody, alanine transaminase activity, and IFN-β were monitored after vaccination. Results Mn2+ promoted IFN-α and IFN-β production in mouse hepatocytes and kuppfer cells. Mn2+ failed to promote IFN-α and IFN-β production in kuppfer cells deficient in STING. Mn2+ promoted activation/phosphorylation of TBK1 and IRF3 during AAV-HBV infection. Mn2+ decreased serum levels of HBsAG, increased serum levels of alanine aminotransferase (ALT), IFN-α and IFN-β, and enhanced lymphocyte infiltration and the percentage of IFN-γ-producing CD8+ T cells in the liver of AAV-HBV-infected mice. In contrast, Mn2+ treatment did not affect serum levels of HBsAG, ALT, IFN-α, or IFN-β in STING-deficient mice. Conclusions Mn2+ promoted HBsAG antibody, ALT, and IFN-β production after HBsAG immunization. Mn2+ promoted type I IFN production in AAV-HBV infection and HBsAG immunization and could be used as an adjuvant for vaccination. [ABSTRACT FROM AUTHOR]

High expression of small proline-rich protein 1A (SPRR1A) has been shown to be associated with tumor prognosis; however, the association between SPRR1A expression and colon cancer prognosis remains unclear. The present study sought to evaluate the association between SPRR1A expression and the clinicopathological characteristics of colon cancer, and to examine its potential prognostic value. A total of 114 patients with colon cancer were included. SPRR1A expression was evaluated by immunohistochemical staining, and the association between SPRR1A expression and clinicopathological parameters was analyzed. The prognostic value of SPRR1A was analyzed by Cox regression analysis, the Oncomine database and the R2 platform. SPRR1A expression was significantly increased in cancerous tissues compared with that in adjacent non-cancerous tissues. SPPRR1A expression was significantly associated with lymph node invasion. High SPRR1A expression was significantly associated with worse overall and disease-free survival rate. Cox regression analysis revealed that T stage, pathological N stage and high SPRR1A expression remained independent predictors for overall survival rate. The Oncomine database analysis demonstrated that SPRR1A mRNA expression levels were significantly increased in colorectal cancer tissues compared with those in adjacent non-cancerous tissues, and high SPRR1A expression was associated with a significantly worse event- and relapse-free survival time in the R2 platform. The data indicate that SPRR1A may serve as a potential biomarker for the prognosis of colon cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the role of colony-stimulating factor 2 (CSF2) in chemotherapy resistance, prognosis, and immune response and to identify its possible mechanisms underlying drug resistance. Methods: Drug-resistant cell lines were obtained by successively increasing drug concentration. RNA-Seq was performed to screen hub genes. CSF2 expression was analyzed via immunohistochemistry. Moreover, The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) dataset, and R2 platform were used to explore the correlations among CSF2 expression, prognosis, and immune response. Results: RNA-Seq indicated that microRNAs in cancer, P53 signaling pathway, and cell cycle were associated with FOLFOX chemotherapy resistance. Protein-protein interaction (PPI), molecular complex detection (MOCDE), and qRT-PCR analysis verified CSF2 as the hub gene in chemotherapy resistance. Moreover, CSF2 expression was lower in the normal tissue than in the cancerous tissue (P<0.05). Higher expression of CSF2 was associated with poor OS and DFS in colon cancer patients (P<0.05). We further found similar results in the Oncomine database and R2 platform (P<0.05). A higher expression of CSF2 in the CRC tissue may be caused by demethylation, which was verified using the TCGA datasets. Moreover, GSEA demonstrated that CSF2 was associated with immune response, which was consistent with results reported using TIMER datasets. Conclusion: CSF2 is a novel biomarker and a prognostic factor for the survival of CRC patients affecting the immune response, and an overexpression of CSF2 in CRC patients may be caused by DNA demethylation. [ABSTRACT FROM AUTHOR]

The process of liver fibrosis is reversible and involves a recovery phase. In the present study, the potential side effects of combination leflunomide and methotrexate (LEF+MTX), a conventional rheumatoid arthritis therapy used in the resolution of liver fibrosis, was investigated. In a carbon tetrachloride-induced liver fibrosis model, the results of hepatic pathology demonstrated that the LEF+MTX combination delayed the recovery of fibrosis, although the activation of hepatic stellate cells in vitro was inhibited. A total of four liver fibrosis-associated indicators, hyaluronic acid, laminin, procollagen type III and collagen IV, maintained high levels in the serum of LEF+MTX-treated mice, while detection of bone marrow-driven monocytes in the blood by flow cytometry indicated that they were significantly decreased. Notably, the results of immunofluorescence staining of hepatic myeloid cells and detection of vascular growth factor A (VEGF-A) in blood and liver suggested that the reduced degeneration of collagen in liver sinusoids was associated with decreased myeloid cell adhesion and the downregulation of VEGF-A in the liver. The present results suggested that in certain cases, treatment with LEF+MTX may impede the recovery of hepatic fibrosis-associated diseases in mice. [ABSTRACT FROM AUTHOR]

The lack of effective medical treatment for advanced stages of gastric cancer mainly contributes to the high mortality rate. The association of forkhead box protein A1 (FOXA1) with tumor progression has been reported in different human cancers. However, the function of FOXA1 in gastric cancer is largely unknown. In the present study, FOXA1 protein showed a significant reduction in gastric cancer samples comparing with matched control samples. In addition, the higher expression of FOXA1 in transcription level was observed in gastric cancer cell lines as compared with that in normal gastric cell line, while the contrary result was observed in protein level. Then we studied the effects of FOXA1 on gastric cancer cells in vitro and in vivo based on FOXA1-overexpression AGS cells. We found that up-regulation of FOXA1 was notably inhibited the cell proliferation and tumor formation, and induced cell apoptosis. Moreover, overexpression of FOXA1 was able to increase the E-cadherin protein level and decreased the Vimentin protein level, which implicates that FOXA1 probably plays as an inhibitor of epithelial mesenchymal transition. In conclusion, these data suggests that FOXA1 may function as a novel anti-oncogene in gastric cancer cells. [ABSTRACT FROM AUTHOR]

Background/Aims Gastric cancer is the third leading cause of cancer-related deaths in the world with high mortality rate due to the lack of markers in early detection and effective therapies. MicroRNAs (miRNAs), a critical part of epigenetic regulations in tumor, have been shown to be closely related to the initiation, development, invasion, metastasis and prognosis of gastric cancer. The present study aims to investigate the expression of miR-1290 in gastric tumor cells and to elucidate the target gene of miR-1290 in SGC-7901 gastric cancer cells. Methodology The fluorescence in situ hybridization, real time PCR and Western blot were used to investigate the expression of miR-1290 in gastric tumor cells and clinical gastric tumor samples. The effect of miR-1290 expression on gastric tumor cells was studied using Synthetic miR-1290 inhibitor transfection, in vitro wound healing assay and flow cytometry analysis. Bioinformatics and Luciferase reporter assay were used to predict and validate the target gene of miR-1290. Results Our results revealed that miR-1290 was highly expressed in SGC-7901 gastric cancer cells as well as in clinical gastric cancer samples, which was correlated with clinical stages, depth of invasion and lymph node metastasis. Synthetic miR-1290 inhibitor transfection significantly inhibited the proliferation and migration of SGC-7901 cells. Bioinformatics analysis and luciferase reporter assay suggested that miR-1290 functioned in gastric cancer cells by targeting FOXA1 gene. Conclusion miR-1290 promotes gastric tumor cells proliferation and metastasis through FOXA1 , which could be used as a marker for diagnosis and a target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Overexpression of Frizzled-7 (FZD7) has been associated with tumor invasion and distant metastases, but little is known about the relationship between FZD7 expression and prognosis in colon cancer. A total of 114 patients with colon cancer between June 2010 and December 2010 were enrolled in this study. The expression of FZD7 in cancerous and adjacent non-cancerous tissues was determined by immunohistochemistry, and the association between FZD7 expression and patient's clinicopathological characteristics was explored. The correlation between FZD7 expression and prognosis of colon cancer patients was analyzed using the Oncomine database and R2. FZD7 expression levels were significantly higher in colon cancer tissues compared with adjacent non-cancerous tissues (P < 0.001). High expression of FZD7 was significantly associated with metastatic or recurrent disease in colon cancer (P = 0.010). Kaplan-Meier survival analysis demonstrated that colon cancer patients with high expression of FZD7 had a significantly poorer OS (P = 0.013) and DFS (P = 0.010). Cox regression demonstrated that the expression of FZD7 was an independent prognostic factor for DFS (HR = 6.647, P = 0.023). A meta-analysis from the Oncomine database demonstrated that FZD7 mRNA levels were significantly higher in colorectal cancer tissues than in normal colorectal tissues, and FZD7 high expression was associated with a significantly poorer event and relapse-free survival time by analyzing the data from the R2: Genomics Analysis and Visualization Platform. Overexpression of FZD7 was associated with poor survival in patients with colon cancer. Our data suggest that FZD7 expression could be an effective prognostic biomarker for colon cancer. [ABSTRACT FROM AUTHOR]

• GEM treatment induces tumor cell apoptosis and PD-L1 expression. • GEM treatment also increases CD8+ and CD4+ T cells proportion. • Combination therapy with GEM and αPD-1 not only has strong anti-tumor effect. Lung cancer is leading cause of cancer death in the world. Chemotherapy is currently one of the standard treatments for lung cancer. Gemcitabine is a pyrimidine nucleoside drug which has been approved by FDA to treat lung cancer. However, acquired resistance inevitable develops after Gemcitabine treatment, limiting clinical efficacy. Lewis lung carcinoma (LLC) cells were treated with Gemcitabine and cell apoptosis and programmed cell death-ligand 1 (PD-L1) expression were analyzed by flow cytometry. LLC mouse model was established to analysis the proportion and programmed cell death-1 (PD-1) expression of CD8 + T cells. Anti-tumor effect by treating with Gemcitabine and anti-PD-1 antibody was measured through in vivo LLC mouse model. Gemcitabine treatment induces tumor cell apoptosis and PD-L1 expression. Further study showed that Gemcitabine treatment also increases CD8+ and CD4+ T cells proportion, PD-1 and PD-L1 expression in LLC mouse model. Combination therapy with Gemcitabine and αPD-1 not only has strong anti-tumor effect, but also could inhibit postsurgical recurrence of LLC. Our findings demonstrated that the combination therapy of Gemcitabine and αPD-1 is an effective therapeutic strategy for lung cancer. [ABSTRACT FROM AUTHOR]