Faculty Collaboration Database

LIGHT Elevation Enhances Immune Eradication of Colon Cancer Metastases. Cancer Res 2017 Apr 15;77(8):1880-1891

Date

03/03/2017

Pubmed ID

28249900

Pubmed Central ID

PMC5410174

DOI

10.1158/0008-5472.CAN-16-1655

Scopus ID

2-s2.0-85018852769 (requires institutional sign-in at Scopus site)   32 Citations

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.

Author List

Qiao G, Qin J, Kunda N, Calata JF, Mahmud DL, Gann P, Fu YX, Rosenberg SA, Prabhakar BS, Maker AV

Author

Jed Calata MD Assistant Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Colonic Neoplasms
Female
HEK293 Cells
Humans
Liver Neoplasms
Lymphocyte Activation
Lymphocytes, Tumor-Infiltrating
Mice
Mice, Inbred BALB C
T-Lymphocytes
Tumor Necrosis Factor Ligand Superfamily Member 14