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Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma

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Tumor Biology

Abstract

The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor microenvironment raises the question why renal cell carcinoma (RCC) progresses. Numerous studies support the implication of CD4+CD25high regulatory T (Treg) cells in RCC development. We aimed in this study to characterize the phenotype and function of circulating and intratumoral Treg cells of RCC patient in order to evaluate their implication in the inhibition of the local antitumor immune response. Our results demonstrate that the proportion of Treg in TIL was, in average, similar to that found in circulating CD4+ T cells of patients or healthy donors. However, intratumoral Treg exhibit a marked different phenotype when compared with the autologous circulating Treg. A higher CD25 mean level, HLA-DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral Treg, suggesting therefore that these cells are effector in the tumor microenvironment. Additionally, intratumoral Treg showed a higher inhibitory function on autologous CD4+CD25− T cells when compared with circulating Treg that may be explained by an overexpression of FoxP3 transcription factor. These findings suggest that intratumoral Treg could be major actors in the impairment of local antitumor immune response for RCC patients.

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Acknowledgments

This work was financially supported by the “PHC Utique” program of the French Ministry of Foreign Affairs and Ministry of higher education and research and the Tunisian Ministry of higher education and scientific research in the CMCU project number 13G0819.

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Authors and Affiliations

  1. Laboratoire de Génétique, d’Immunologie et de pathologies humaines, Faculté des Sciences de Tunis, Campus Universitaire El Manar, Tunis, Tunisia

    Gati Asma, Gorrab Amal, Marrakchi Raja & Ben Ammar Elgaaied Amel

  2. Service d’Urologie, Hôpital Charles Nicolle, Tunis, Tunisia

    Derouiche Amine & Chebil Mohammed

  3. Department de biologie, Faculté des sciences de Tunis, Tunis, Tunisia

    Gati Asma

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  1. Gati Asma
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  2. Gorrab Amal
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  5. Chebil Mohammed
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  6. Ben Ammar Elgaaied Amel
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Correspondence to Gati Asma.

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Asma, G., Amal, G., Raja, M. et al. Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma. Tumor Biol. 36, 3727–3734 (2015). https://doi.org/10.1007/s13277-014-3012-8

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  • DOI: https://doi.org/10.1007/s13277-014-3012-8

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