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Determination of a CD4+CD25−FoxP3+ T cells subset in tumor-draining lymph nodes of colorectal cancer secreting IL-2 and IFN-γ

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Tumor Biology

Abstract

CD4+CD25−FoxP3+ cells are a newly recognized subset of T cells which was first reported in autoimmune diseases. In our previous study, this subset was detected in tumor-draining lymph nodes (TDLNs) of patients with breast cancer. As little is known about their function in TDLNs of cancer patients, in this study, their frequency as well as their ability to produce interleukin (IL)-2, IL-10, or interferon (IFN)-γ were investigated in TDLNs of colorectal cancer (CRC) patients. Mononuclear cells were isolated from lymph nodes of 13 patients with CRC using Ficoll-Hypaque gradient centrifugation. Cells were stimulated in vitro and stained with CD25, CD4, FoxP3, IFN-γ, IL-10, and IL-2 or isotype matched antibodies and subjected to flow cytometry. The frequency of CD4+CD25−FoxP3+CD127dim/− cells was significantly lower than CD4+CD25+FoxP3+CD127dim/− population in TDLNs of CRC patients. The percentage of CD127dim/− cells and also the MFI of FoxP3 expression was significantly lower in CD4+CD25−FoxP3+ in comparison with CD4+CD25+FoxP3+ population. Moreover, CD4+CD25−FoxP3+ cells contained higher percentages of IL-2- and IFN-γ-producing cells than CD4+CD25+FoxP3+ subpopulation. But, no difference was seen between two subsets in terms of IL-10 production. CD4+CD25−FoxP3+ cells in TDLNs of CRC patients had lower suppressive and higher effector properties in comparison with CD4+CD25+FoxP3+ conventional regulatory T cells.

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Acknowledgments

This study was financially supported by Shiraz Institute for Cancer Research (Grant No. ICR-100-508). The study was also part of MSc thesis project of Morteza Jafarinia, Department of Immunology, Shiraz University of Medical Sciences (Grant No. 93-7192).

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Authors and Affiliations

  1. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71345-1798, Shiraz, Iran

    Morteza Jafarinia, Fereshteh Mehdipour & Abbas Ghaderi

  2. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Morteza Jafarinia & Abbas Ghaderi

  3. Colorectal Research Center, Faghihi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Vahid Hosseini & Leila Ghahramani

  4. Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Masood Hosseinzadeh

Authors
  1. Morteza Jafarinia
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  2. Fereshteh Mehdipour
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  3. Seyed Vahid Hosseini
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  4. Leila Ghahramani
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  5. Masood Hosseinzadeh
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  6. Abbas Ghaderi
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Corresponding author

Correspondence to Abbas Ghaderi.

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Written informed consents were obtained from all patients, and the study was approved by the Ethics Committee of Shiraz University of Medical Sciences.

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Morteza Jafarinia and Fereshteh Mehdipour have equal contributions to the study.

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Jafarinia, M., Mehdipour, F., Hosseini, S.V. et al. Determination of a CD4+CD25−FoxP3+ T cells subset in tumor-draining lymph nodes of colorectal cancer secreting IL-2 and IFN-γ. Tumor Biol. 37, 14659–14666 (2016). https://doi.org/10.1007/s13277-016-5345-y

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  • DOI: https://doi.org/10.1007/s13277-016-5345-y

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