LIGHT Elevation Enhances Immune Eradication of Colon Cancer Metastases
| Autor: | Jianzhong Qin, Dolores Mahmud, Peter H. Gann, Jed F. Calata, Bellur S. Prabhakar, Steven A. Rosenberg, Guilin Qiao, Nicholas Kunda, Yang Xin Fu, Ajay V. Maker |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research Colorectal cancer medicine.medical_treatment T-Lymphocytes Disease Lymphocyte proliferation Lymphocyte Activation Mice 0302 clinical medicine Cytotoxic T cell 2.1 Biological and endogenous factors Lymphocytes Aetiology Inbred BALB C Cancer Mice Inbred BALB C Tumor Liver Disease Liver Neoplasms Colo-Rectal Cancer Cytokine 030220 oncology & carcinogenesis Colonic Neoplasms Female Infiltration (medical) medicine.medical_specialty Tumor Necrosis Factor Ligand Superfamily Member 14 Oncology and Carcinogenesis Article Cell Line 03 medical and health sciences Lymphocytes Tumor-Infiltrating Immune system Rare Diseases Cell Line Tumor Internal medicine medicine Animals Humans Tumor-Infiltrating Oncology & Carcinogenesis business.industry Inflammatory and immune system medicine.disease 030104 developmental biology HEK293 Cells Cell culture business Digestive Diseases |
| Zdroj: | Cancer research, vol 77, iss 8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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