NK cells direct the perspective approaches to cancer immunotherapy.

Natural killer (NK) cells are innate immune cells with cytotoxic potentials to kill cancerous cells in several mechanisms, which could be implied for cancer therapy. While potent, their antitumor activities specially for solid tumors impaired by inadequate tumor infiltration, suppressive tumor microenvironment, cancer-associated stroma cells, and tumor-supportive immune cells. Therefore, manipulating or reprogramming these barriers by prospective strategies might improve current immunotherapies in the clinic or introduce novel NK-based immunotherapies. NK-based immunotherapy could be developed in monotherapy or in combination with other therapeutic regimens such as oncolytic virus therapy and immune checkpoint blockade, as presented in this review.

Cancer Stem Cells in Colorectal Cancer: Implications for Targeted Immunotherapies.

PURPOSE: Colorectal cancers are composed of heterogeneous cell populations in the concepts of genetic and functional degrees that among them cancer stem cells are identified with their self-renewal and stemness capability mediating primary tumorigenesis, metastasize, therapeutic resistance, and tumor recurrence. Therefore, understanding the key mechanisms of stemness in colorectal cancer stem cells (CRCSCs) provides opportunities to discover new treatments or improve existing therapeutic regimens. METHODS: We review the biological significance of stemness and the results of potential CRCSC-based targeted immunotherapies. Then, we pointed out the barriers to targeting CRCSCs in vivo and highlight new strategies based on synthetic and biogenic nanocarriers for the development of future anti-CRCSC trials. RESULTS: The CSCs' surface markers, antigens, neoantigens, and signaling pathways supportive CRCSCs or immune cells that are interacted with CRCSCs could be targeted by immune monotherapy or in formulation with developed nanocarriers to overcome the resistant mechanisms in immune evader CRCSCs. CONCLUSION: Identification molecular and cellular cues supporting stemness in CRCSCs and their targeting by nanoimmunotherpy can improve the efficacy of existed therapies or explore novel therapeutic options in future.

Characterizing the oncogenic importance and exploring gene-immune cells correlation of ACTB in human cancers.

After cardiovascular diseases, cancer is the second deadliest malignancy in the world. The current study was launched to investigate the diagnostic and prognostic landscape of Beta-actin (ACTB) via a multi-layered bioinformatics approach. ACTB expression was analyzed and validated via UALCAN, TIMER, GENT2, GEPIA, and HPA. ACTB promoter methylation was evaluated via MREXPRES. Furthermore, ACTB prognostic values and their correlation with cancer metastasis were explored through the KM plotter and TNMplot, respectively. Then, cBioPortal, CancerSEA, Enrichr, TIMER, MuTarget, and CDT were used to analyze ACTB-related genetic alterations, transcription factors (TFS), MicroRNAs (miRNAs), chemotherapeutic drugs, and the correlation between its expression, immune cells, and different other parameters. We found that ACTB expression was remarkably higher in 24 major human cancer tissues than the normal samples. Additionally, elevated ACTB expression was associated with poorer survival and metastasis in only liver hepatocellular carcinoma (LIHC), head and neck squamous cancer (HNSC), and lung adenocarcinoma (LUAD). This implies that ACTB plays a significant role in the development and progression of LIHC, HNSC, and LUAD. Furthermore, enrichment analysis showed that ACTB-associated genes regulate different Biological Processes (BP), Molecular Functions (MF), and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. Moreover, ACTB up-regulation had interesting correlations with immune infiltration of CD4+ T, and CD8+ T, tumor purity, mutant genes, and a few other important parameters. At last, via this study, we also explored ACTB-associated clinically important expression regulators, including TFS, miRNAs, and different chemotherapeutic drugs. The results of the present study suggested that ACTB might be a potential candidate biomarker in LIHC, HNSC, and LUAD.

Estimation of hub genes and exploration of multi-omics level alterations in the landscape of lung adenocarcinoma.

OBJECTIVES: Lung adenocarcinoma (LUAD) is recognized as one of the most prevalent and deadliest malignancies around the globe. The molecular mechanisms behind LUAD have not been fully elucidated. This study was launched to explore LUAD-associated hub genes and their enriched pathways using bioinformatics methods. METHODS: Information on GSE10072 was retrieved from the Gene Expression Omnibus (GEO) database and analyzed via the Limma package-based GEO2R tool to obtain the top 100 differentially expressed genes (DEGs) in LUAD. The protein-protein interaction (PPI) network of the DEGs was drawn using the STRING website and was shifted into Cytoscape to screen the top 6 hub genes via the CytoHubba application. Furthermore, the expression analysis and validation of hub genes in LUAD samples and cell lines were done using UALCAN, OncoDB, and GENT2 databases. Moreover, OncoDB was also used for analyzing hub gene DNA methylation levels. In addition, cBioPortal, GSEA tool, Kaplan-Meier (KM) plotter, Enrichr, CancerSEA, and DGIdb were performed to explore some other important aspects of hub genes in LUAD. RESULTS: We identified Interleukin 6 (IL6), Collagen, type I, alpha 1 (COL1A1), TIMP metallopeptidase inhibitor 1 (TIMP1), CD34 molecule (CD34), Decorin (DCN), and Secreted Phosphoprotein 1 (SPP1) genes as the hub genes in LUAD, out of which IL6, CD34, and DCN were significantly down-regulated while COL1A1, TIMP1, and SPP1 were significantly up-regulated in LUAD cell lines and samples of diverse clinical variables. In this study, we also documented some important correlations between hub genes and other parameters such as DNA methylation, genetic alterations, Overall Survival (OS), and 14 important states at the single cell level. Lastly, we also identified hub genes associated with the ceRNA network and 11 important chemotherapeutic drugs. CONCLUSION: We identified 6 hub genes involved in the development and progression of LUAD. These hub genes can also be helpful in the accurate detection of LUAD and provide novel ideas for treatment.

Phosphatidylinositol 3-kinase signaling pathway and inflammatory bowel disease: Current status and future prospects.

Inflammatory bowel disease (IBD) is a chronic life-limiting disease of gastrointestinal tract characterized by widespread enteric inflammation. IBD is a multifactorial disease, and different environmental, microbial, and immune-related factors give rise to the development of disease. Among several factors, the preponderance of pro-inflammatory T helper 17 cells over the anti-inflammatory regulatory T cells augments inflammation in the intestinal mucosa. Prevailing evidence accentuates that PI3K signaling pathway plays a central role in the pathophysiology of the condition by regulating the inflammatory process in the gut mucosa. By recognizing the implications of PI3K in the pathogenesis of IBD, agents that could modulate this pathway have recently been at the focus of research, yielding encouraging results mainly in the experimental IBD models. In this review, we have summarized the recent advances, which may hold the keys to identify novel therapeutic strategies for IBD.