title: Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma.
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(+)CD25(high) 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.
authors.affiliation: Laboratoire de Génétique, d'Immunologie et de pathologies humaines, Faculté des Sciences de Tunis, Campus Universitaire El Manar, Tunis, Tunisia, asmagati@yahoo.fr.
authors.forename: Gati
authors.initials: G
authors.lastname: Asma
authors.forename: Gorrab
authors.initials: G
authors.lastname: Amal
authors.forename: Marrakchi
authors.initials: M
authors.lastname: Raja
authors.forename: Derouiche
authors.initials: D
authors.lastname: Amine
authors.forename: Chebil
authors.initials: C
authors.lastname: Mohammed
authors.forename: Ben Ammar Elgaaied
authors.initials: BA
authors.lastname: Amel
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D007680:Kidney Neoplasms / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors