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

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Title: Shedding LIGHT (TNFSF14) on the tumor microenvironment of colorectal cancer liver metastases
Author(s): Qin, Jian Zhong; Upadhyay, Vivek; Prabhakar, Bellur; Maker, Ajay V.
Subject(s): Colorectal liver metastases Immunotherapy LIGHT Tumor infiltrating lymphocytes
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.
Issue Date: 2013-03
Publisher: BioMed Central
Citation Info: Qin, J. Z., Upadhyay, V., Prabhakar, B. and Maker, A. V. Shedding LIGHT (TNFSF14) on the tumor microenvironment of colorectal cancer liver metastases. Journal of Translational Medicine. 2013. 11. DOI: 10.1186/1479-5876-11-70
Type: Article
Description: © 2013 by BioMed Central , Journal of Translational Medicine. © 2013 Qin et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
URI: http://hdl.handle.net/10027/11152
ISSN: 1479-5876
Sponsor: Warren and Clara Cole Career Development Award, the UIC Cancer Center Cancer Junior Investigator Pilot Grant, and the AIMMC Creticos Cancer Center Research Grant.
Date Available in INDIGO: 2014-02-10
 

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