Inflammation in the Tumor Microenvironment

Inflammation in the Tumor Microenvironment Qing Lin,1 Shi Jin,2 Mei Han,3 Wenxin Zheng,4 Jiaming Liu,5 and Xiaolong Wei6 1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 2Division of Gastroenterology, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA 3McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 4Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA 5Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China 6Shantou University Medical College, Shantou, Guangdong 515041, China Correspondence should be addressed to Qing Lin; ude.imhj@2nilq and Jiaming Liu; moc.liamtoh@rdgnimaijuil Received 18 March 2018; Accepted 18 March 2018; Published 24 June 2018 Copyright © 2018 Qing Lin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The objective of this special issue is to provide a better understanding of the tumor-associated inflammatory signaling and their microenvironmental cross talk and network, which is crucial for elucidating tumorigenesis mechanisms and for cancer therapy, prevention, and risk assessment. A substantial number of manuscripts were submitted, and after a thorough peer review process, eleven papers were accepted for inclusion in this special issue. These papers investigate the involvements of the essential microenvironmental elements including inflammatory mediators and cellular effectors in the context of cancer-related inflammatory processes; they also offer new insights into tumor immunotherapy, which will help explore new targets or approaches for cancer treatment, by either boosting antitumor immunity or disrupting tumor-educated immunosuppression. The paper by S. Ye et al. investigates the immunoregulatory properties of enavatuzumab, a humanized anti-TWEAK receptor monoclonal antibody. This preclinical study demonstrates that enavatuzumab exerted its potent antitumor activity by actively recruiting and activating myeloid effectors to kill tumor cells. The findings of enavatuzumab-induced chemokines warrant further evaluation in clinical studies as potential biomarkers for such activity. The paper by M. Janiczek et al. presents a systematic review on immunotherapy as a promising treatment for prostate cancer. The authors summarize the recent advances and trends on three categories of immunotherapies: checkpoint inhibitors, cytokines, and therapeutic cancer vaccines, providing better understanding on the complexity of tumor cells and their interactions with the surrounding inflammatory microenvironment. The paper by W. Zeng et al. tries to dissect the mechanism underlying the effects of methylation agent decitabine (DAC) treatment on myeloid myelodysplastic syndromes (MDS) by in vitro study with the MDS cell line SKM-1. Their results show that DAC could rescue FOXO3A, a potentially tumor-suppressive transcription factor. The reactivation of FOXO3 signaling is also critical for the anti-MDS therapeutic effects of DAC. The paper by M. Liu et al. conducts bioinformatics analysis on differentially expressed genes (DEGs) between tumor samples and normal samples to identify key genes and pathways in glioma. Some identified hub genes may be important for regulating inflammatory responses, and CDK17, GNA13, PHF21A, and MTHFD2 might be important and potentially valuable in the prognosis and treatment of glioma. These identified genes and pathways would provide a more detailed molecular mechanism for underlying glioma initiation and development. The paper by G.-Y. Liou focuses on cytokine signaling of tumor-facilitated immune cells and of cancer cells that lead to tumor initiation, progression, and metastasis of pancreatic cancer and prostate cancer. The review of the complex cytokine network among tumor cells, immune cells, and other types of cells including stromal cells and endothelial cells would provide information on developing effective immunotherapies for treating related tumors. The paper by G. D’Arena et al. summarizes published data on the prognostic significance of regulatory T cells in hematological malignancies. The authors attribute the variability reported by different groups to the heterogeneity of the experimental approaches, and emphasize the need to apply standardized approaches in the study of regulatory T cells in hematological malignancies and in cancer in general. S. Chen et al. conducted a large cohort study to validate the involvement of four genes, STAT1, IGF1, RAC1, and MDM2, in the recurrence of a giant-cell tumor of the bone. Their findings suggest the potential of thes (...truncated)