title: Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade.
abstract: BACKGROUND
  Sub-lethal doses of ionizing radiation (IR) can alter the phenotype of target tissue by modulating genes that influence effector T cell activity. Previous studies indicate that cancer cells respond to radiation by up-regulating surface expression of death receptors, cell adhesion molecules and tumor-associated antigens (TAA). However, there is limited information available regarding how T cells themselves are altered following these interactions with irradiated tumor cells.
  
  
  METHODS
  Here, several human colorectal tumor cell lines were exposed to radiation (0-10 Gy) in vitro and changes in the expression of molecules costimulatory to effector T cells (4-1BBL, OX-40L, CD70, ICOSL) were examined by flow cytometry. T cell effector function was assessed to determine if changes in these proteins were directly related to the changes in T cell function.
  
  
  RESULTS
  We found OX-40L and 4-1BBL to be the most consistently upregulated proteins on the surface of colorectal tumor cells post-IR while ICOSL and CD70 remained largely unaltered. Expression of these gene products correlated with enhanced killing of irradiated human colorectal tumor cells by TAA-specific T-cells. Importantly, blocking of both OX-40L and 4-1BBL reversed radiation-enhanced T-cell killing of human tumor targets as well as T-cell survival and activation.
  
  
  CONCLUSIONS
  Overall, results of this study suggest that, beyond simply rendering tumor cells more sensitive to immune attack, radiation can be used to specifically modulate expression of genes that directly stimulate effector T cell activity.
authors.affiliation: Department of Biology, Georgia State University, 161 Jesse Hill Jr. Dr, Atlanta, GA, 30303, USA. akumari1@student.gsu.edu.
authors.forename: Anita
authors.initials: A
authors.lastname: Kumari
authors.affiliation: Department of Biology, Georgia State University, 161 Jesse Hill Jr. Dr, Atlanta, GA, 30303, USA. cgarnettbenson@gsu.edu.
authors.forename: Charlie
authors.initials: C
authors.lastname: Garnett-Benson
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism*; D053282:CD27 Ligand / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D016923:Cell Death / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D009077:Mucins / Q000378:metabolism; D053278:OX40 Ligand / Q000378:metabolism*; D011839:Radiation, Ionizing; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000528:radiation effects
chemical_list: D053330:4-1BB Ligand; D053282:CD27 Ligand; D002272:Carcinoembryonic Antigen; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D009077:Mucins; D053278:OX40 Ligand