Published in:
01-09-2006
Ex-Vivo Analysis of CD8+ T Cells Infiltrating Colorectal Tumors Identifies a Major Effector-Memory Subset with Low Perforin Content
Authors:
SHENG-WEI YE, YU WANG, DANILA VALMORI, MAHA AYYOUB, YAN HAN, XIAO-LAN XU, AI-LIAN ZHAO, LI QU, SACHA GNJATIC, GERD RITTER, LLOYD J. OLD, JIN GU
Published in:
Journal of Clinical Immunology
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Issue 5/2006
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Abstract
Previous studies have indicated that the infiltration of CD8+ T cells in colorectal cancer is an independent predictor of increased survival but clinical observations have suggested that the cytotoxic function of CD8+ T cells infiltrating colorectal cancer may often be limited. In this study, we have assessed the phenotype of colorectal cancer CD8+ tumor-infiltrating lymphocytes (TILs) isolated ex vivo from tumor tissue, and assessed the perforin content of TIL with respect to their location using immunohistochemistry. We found that CD8+ T cells TILs isolated from colorectal cancer are mainly composed of antigen-experienced cells of effector memory type (TEM, CD45RA-CCR7−, and CD27+/CD28− or CD27−/CD28−), and contain only minor proportions of terminally differentiated CD8+ T cells (TEMRA, CD45RA+CCR7−). The perforin content of these TILs, however, is significantly lower than that of antigen-experienced T cells in PBMCs due to the much lower levels of perforin found in the CD27-CD28− subset in TILs compared with CD8+ T cells of similar phenotype in PBMCs.