Characterization of the Neuroendocrine Tumor Immune Microenvironment
PANCREAS
Authors: da Silva, Annacarolina; Bowden, Michaela; Zhang, Sui; Masugi, Yohei; Thorner, Aaron R.; Herbert, Zachary T.; Zhou, Chensheng Willa; Brais, Lauren; Chan, Jennifer A.; Hodi, F. Stephen; Rodig, Scott; Ogino, Shuji; Kulke, Matthew H.
Abstract
Objectives The immune environment and the potential for neuroendocrine tumors (NETs) to respond to immune checkpoint inhibitors remain largely unexplored. We assessed immune checkpoint marker expression, lymphocytic infiltrate, and associated mutational profiles in a cohort of small intestine and pancreatic NETs. Methods We assessed expression of PDCD1 (PD-1), CD274 (PD-L1), and PDCD1LG2 (PD-L2) in archival tissue from 64 small intestine (SINETs) and 31 pancreatic NETs (pNET). We additionally assessed T-cell infiltrates, categorizing T-cell subsets based on expression of the T-cell markers CD3, CD8, CD45RO (PTPRC), or FOXP3. Finally, we explored associations between immune checkpoint marker expression, lymphocytic infiltrate, and tumor mutational profiles. Results Expression of PD-1 or PD-L1 in small intestine or pancreatic NET was rare, whereas expression of PD-L2 was common in both NET subtypes. T-cell infiltrates were more abundant in pNET than in SINET. We found no clear associations between immune checkpoint marker expression, immune infiltrates, and specific mutational profile within each tumor type. Conclusions Our findings provide an initial assessment of the immune environment of well-differentiated NETs. Further studies to define the immunologic differences between pNET and SINET, as well as the role of PD-L2 in these tumors, are warranted.
Microarray data analysis to identify differentially expressed genes and biological pathways associated with asthma
EXPERIMENTAL AND THERAPEUTIC MEDICINE
Authors: Qi, Shanshan; Liu, Guanghui; Dong, Xiang; Huang, Nan; Li, Wenjing; Chen, Hao
Abstract
The present study aimed to identify differentially expressed genes (DEGs) and biological processes (BPs) associated with asthma. DEGs between allergic asthma and healthy controls were screened from GSE15823. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction network was constructed, followed by module mining and functional analysis. Additionally, GSE41649 was downloaded to validate the reliability of the results. In GSE41649, DEGs were identified and compared with key DEGs identified in GSE15823. A total of 43 upregulated and 275 downregulated DEGs were obtained from GSE15823. Upregulated DEGs, such as nitric oxide synthase 2 (NOS2), were enriched in BPs related to oxidation reduction. Downregulated DEGs, such as chemokine (C-C motif) ligand 19 (CCL21) and Cys-X-Cys ligand (CXCL9), were enriched in immune response-related BPs. Protein tyrosine phosphatase receptor type C (PTPRC), CCL21, and CXCL9 were identified as hub genes. The DEGs in module 1 were significantly involved in the chemokine signaling pathway (P<0.05). The expression of the key genes obtained in GSE15823 demonstrated the same variation directions in the two datasets. The immune response, oxidants and nitric oxide metabolic pathways may have important roles in the progression of asthma. DEGs of PTPRC, CCL21, CXCL9 and NOS2 may be the potential targets for asthma diagnosis and treatment.