6533b82afe1ef96bd128b827
RESEARCH PRODUCT
Human ectonucleotidase-expressing CD25 high Th17 cells accumulate in breast cancer tumors and exert immunosuppressive functions
Frédérique VégranFrançois GhiringhelliValentin DerangèreEmeric LimagneRomain BoidotLionel ApetohMarion ThibaudinSylvain LadoireHélène BergerMarie Chaixsubject
0301 basic medicineAdenosineT cellImmunologyGeneration[SDV.CAN]Life Sciences [q-bio]/Cancerchemical and pharmacologic phenomenaBiology[ SDV.CAN ] Life Sciences [q-bio]/Cancer03 medical and health sciencesInterleukin 21Immune systembreast cancerCancer stem cellmedicineCd73Immunology and AllergyChemotherapy[ SDV.IMM ] Life Sciences [q-bio]/ImmunologyIL-2 receptorRegulatory T-CellsSuppressionCarcinomaFOXP3hemic and immune systemsSuicide gene3. Good healthReceptor Ccr6030104 developmental biologymedicine.anatomical_structurePhenotypeOncologyImmunologyInterleukin 12[SDV.IMM]Life Sciences [q-bio]/ImmunologyTh17prognosisectonucleotidasedescription
IF 7.644; International audience; Th17 cells contribute to the development of some autoimmune and allergic diseases by driving tissue inflammation. However, the function of Th17 cells during cancer progression remains controversial. Here, we show that human memory CD25(high) Th17 cells suppress T cell immunity in breast cancer. Ectonucleotidase-expressing Th17 cells accumulated in breast cancer tumors and suppressed CD4(+) and CD8(+) T cell activation. These cells expressed both Ror gamma t and Foxp3 genes and secreted Th17 related cytokines. We further found that CD39 ectonucleotisase expression on tumor-infiltrating Th17 cells was driven by TGF-beta and IL-6. Finally, immunohistochemical analysis of localized breast cancer revealed that high-tumor infiltration by IL-17(+) cells was associated with a poor clinical outcome and impeded the favorable effect of high CD8(+) infiltration. Altogether, these findings suggest that intratumoral Th17 cells compromise anticancer immune responses in breast cancer patients.
year | journal | country | edition | language |
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2015-07-06 |