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Open Access Research

Shedding LIGHT (TNFSF14) on the tumor microenvironment of colorectal cancer liver metastases

Jian Zhong Qin13, Vivek Upadhyay1, Bellur Prabhakar2 and Ajay V Maker12*

  • * Corresponding author: Ajay V Maker amaker@uic.edu

  • † Equal contributors

Author Affiliations

1 Department of Surgery, University of Illinois at Chicago, Division of Surgical Oncology, 835 S. Wolcott MC790, Chicago, IL 60612, USA

2 Department of Microbiology and Immunology, University of Illinois at Chicago, 835 S. Wolcott, Chicago, IL 60612, USA

3 School of Life Science and Biotechnology, Dalian University, Dalian, China

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Journal of Translational Medicine 2013, 11:70  doi:10.1186/1479-5876-11-70

Published: 20 March 2013

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.

Keywords:
Colorectal liver metastases; Immunotherapy; LIGHT; Tumor infiltrating lymphocytes