title: Shedding LIGHT (TNFSF14) on the tumor microenvironment of colorectal cancer liver metastases.
abstract: BACKGROUND
  T-cell infiltration in primary colon tumors is associated with improved patient survival. Preliminary data supports a similar association in colorectal liver metastases (CRLM), and we previously identified increased CRLM expression of the immunostimulatory cytokine LIGHT (TNFSF14) to be related to improved patient prognosis. Therefore, mechanisms to augment the T-cell response in CRLM may be a promising treatment modality, however, the tumor immune microenvironment and LIGHT expression in CRLM remains to be characterized.
  
  
  METHODS
  Utilizing a syngeneic and immunocompetent model of CRLM, the immune microenvironment was characterized for lymphocyte phenotype, function, and location utilizing flow cytometry, immunoassays, and immunofluorescence microscopy.
  
  
  RESULTS
  CD3+ and CD4+ lymphocytes were decreased, and CD8+ cells were increased in CRLM compared to control liver. When present, greater populations of tumor infiltrating lymphocytes (TIL) were found peritumoral than intratumoral. The TIL expressed significantly higher levels of CD69 and CD107a, but lower levels of LIGHT. Cytokine expression profiles revealed increased levels of the T-helper 1 (Th1) cytokines IFN gamma, IL-12, IL-1b, and IL-8 in CRLM compared to control liver tissue. There was no difference in T-helper 2 (Th2) cytokines between the groups.
  
  
  CONCLUSIONS
  Characterization of the tumor microenvironment of CRLM revealed that although a limited number of activated T-cells infiltrate the tumor and initiate an immune response, the number of LIGHT + T cells infiltrating the tumor were very low. Techniques to decrease suppressive influences or augment the cytotoxic T-cell response are needed and may be possible through mechanisms that can increase intratumoral TIL LIGHT expression.
authors.affiliation: Department of Surgery, University of Illinois at Chicago, Division of Surgical Oncology, 835 S, Wolcott MC790, Chicago, IL 60612, USA.
authors.forename: Jian Zhong
authors.initials: JZ
authors.lastname: Qin
authors.forename: Vivek
authors.initials: V
authors.lastname: Upadhyay
authors.forename: Bellur
authors.initials: B
authors.lastname: Prabhakar
authors.forename: Ajay V
authors.initials: AV
authors.lastname: Maker
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010641:Phenotype; D018418:Th2 Cells / Q000166:cytology; D059016:Tumor Microenvironment; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000378:metabolism*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D052118:Lysosomal-Associated Membrane Protein 1; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D000099192:CD69 Antigens; C505914:TNFSF14 protein, human; C505915:Tnfsf14 protein, mouse