title: [Altered Treg and IL-1A Expression in the Immune Microenvironment  of Lung Squamous-cell Cancer after EGFR Blockade].
abstract: BACKGROUND
  Targeting the mutations and amplifications in the epidermal growth factor receptor (EGFR) gene has curative effects on cancers of the lung, oral cavity, and gastrointestinal system. However, a systemic immune inflammation is an adverse effect of this therapeutic strategy. In this study, we aimed to identify the possible changes in the tumor microenvironment that contribute to the anti-cancer activity of EGFR inhibition.
  
  
  METHODS
  Squamous-cell cancers were induced by the syngeneic transplantation of either EGFR-null or wild-type mouse primary keratinocytes that had been transduced with an oncogenic H-ras retrovirus. The mice were treated with gefinitib. Then, flow cytometric was used to detect the ratio of T cells and the expression of programmed cell death receptor 1 (PD-1). RT-PCR was used to detect the expression of cytokines and chemokines.
  
  
  RESULTS
  Tumors that formed from EGFR-null keratinocytes were smaller, had fewer infiltrating FoxP3+ Treg cells, lower Foxp3 RNA, and lower percentage of PD-1 positive CD4 cells than those formed from wild-type keratinocytes. These results indicated that tumor cells can autonomously regulate the tumor microenvironment. Hosts with wild-type cancers and that were treated with gefitinib for 1 week tended to have smaller tumors. The treated mice in the short-term pharmacological model tended to have reduced FoxP3+ cells and FoxP3 RNA in the tumor microenvironment, as well as a substantially increased ratio of IL-1A/IL-1RA transcripts. These results suggested that the brief systemic inhibition of EGFR signaling alters the immune environment of the targeted cancer.
  
  
  CONCLUSIONS
  The autonomous (genetic) or systemic (pharmacologic) inhibition of EGFR signaling in tumor cells reduces tumor growth and Treg infiltration in the tumor microenvironment. An EGFR-dependent Treg function supports the growth of squamous cancers. Therefore, Treg is a target in the therapeutic strategy of EGFR inhibition.
authors.affiliation: Logistics University of People's Armed Police Force, Tianjin 300162, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: He
authors.affiliation: Hospital Affiliated to Logistics College of  Chinese People's Armed Police Forces, Tianjin 300162, China.
authors.forename: Luyu
authors.initials: L
authors.lastname: Qi
authors.affiliation: Logistics University of People's Armed Police Force, Tianjin 300162, China.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D055786:Gene Knockout Techniques; D053582:Interleukin-1alpha / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology*
chemical_list: D053582:Interleukin-1alpha; D012333:RNA, Messenger; D066246:ErbB Receptors