title: LIGHT Elevation Enhances Immune Eradication of Colon Cancer Metastases.
abstract: The majority of patients with colon cancer will develop advanced disease, with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors that could empower antitumor immune responses in this setting remain to be elucidated. We reported that the immunostimulatory cytokine LIGHT (TNFSF14) in the microenvironment of colon cancer metastases associates with improved patient survival, and here we demonstrate in an immunocompetent murine model that colon tumors expressing LIGHT stimulate lymphocyte proliferation and tumor cell-specific antitumor immune responses. In this model, increasing LIGHT expression in the microenvironment of either primary tumors or liver metastases triggered regression of established tumors and slowed the growth of liver metastases, driven by cytotoxic T-lymphocyte-mediated antitumor immunity. These responses corresponded with significant increases in tumor-infiltrating lymphocytes and increased expression of lymphocyte-homing signals in the metastatic tumors. Furthermore, we demonstrated evidence of durable tumor-specific antitumor immunity. In conclusion, increasing LIGHT expression increased T-cell proliferation, activation, and infiltration, resulting in enhanced tumor-specific immune-mediated tumor regressions in primary tumors and colorectal liver metastases. Mechanisms to increase LIGHT in the colon cancer microenvironment warrant further investigation and hold promise as an immunotherapeutic strategy.Cancer Res; 77(8); 1880-91. ©2017 AACR.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Guilin
authors.initials: G
authors.lastname: Qiao
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kunda
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Jed F
authors.initials: JF
authors.lastname: Calata
authors.affiliation: Department of Hematology and Oncology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Dolores L
authors.initials: DL
authors.lastname: Mahmud
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Peter
authors.initials: P
authors.lastname: Gann
authors.affiliation: Department of Pathology, University of Texas Southwestern, Dallas, Texas.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, Illinois. amaker@uic.edu.|Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Ajay V
authors.initials: AV
authors.lastname: Maker
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000096:biosynthesis* / Q000276:immunology*
chemical_list: C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14