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Ex-Vivo Analysis of CD8+ T Cells Infiltrating Colorectal Tumors Identifies a Major Effector-Memory Subset with Low Perforin Content

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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.

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ACKNOWLEDGEMENTS

This study was supported by Designed Grant of Cancer Research Institute (New York, NY), New Star Program of Science and Technology of Beijing Science and Technology Committee (H020821070130), “211” Program of Peking University, and Science Foundation of Beijing Cancer Hospital

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Authors and Affiliations

  1. Department of Colorectal Surgery, Peking University School of Oncology, Beijing Cancer Hospital, No. 52 Fu-cheng Road, Hai-dian District, Beijing, 100036, P.R. China

    SHENG-WEI YE & JIN GU

  2. Cancer Biological Therapy and Diagnosis Center, Peking University School of Oncology, Beijing Cancer Hospital, No. 52 Fu-cheng Road, Hai-dian District, Beijing, 100036, P.R. China

    YU WANG, YAN HAN, XIAO-LAN XU & LI QU

  3. Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, USA

    AI-LIAN ZHAO

  4. Department of Pathology, Peking University School of Oncology, Beijing Cancer Hospital, Beijing, P.R. China

    DANILA VALMORI, MAHA AYYOUB, SACHA GNJATIC, GERD RITTER & LLOYD J. OLD

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  1. SHENG-WEI YE
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  2. YU WANG
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  3. DANILA VALMORI
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Correspondence to YU WANG or JIN GU.

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YE, SW., WANG, Y., VALMORI, D. et al. Ex-Vivo Analysis of CD8+ T Cells Infiltrating Colorectal Tumors Identifies a Major Effector-Memory Subset with Low Perforin Content. J Clin Immunol 26, 447–456 (2006). https://doi.org/10.1007/s10875-006-9040-4

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  • DOI: https://doi.org/10.1007/s10875-006-9040-4

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