Prognostic significance and mechanism of Treg infiltration in human brain tumors.
Regulatory T cells (Tregs) accumulate in tumors and can contribute to the dismal immune responses observed in these tumors. We reported that the percentage of tumor infiltrating Tregs is strongly correlated with the WHO grade of the brain tumor. We now report on the clinical follow-up of this patient cohort (n=83). Subgroup analyses in patients with glioblastomas (n=29) showed a moderate, not significant, inverted association between Tregs and survival. We further show that Tregs in glioblastomas, in contrast to other tumor infiltrating effector lymphocytes, highly express the CCR4 chemokine receptor. Moreover, the CCR4 ligand CCL22 is secreted by glioblastomas and may explain the specific Treg accumulation seen in these tumors.
Jacobs
Joannes F M
JF
Nijmegen Centre for Molecular Life Sciences, Department of Tumor Immunology, Nijmegen, The Netherlands.
Idema
Albert J
AJ
Bol
Kalijn F
KF
Grotenhuis
J André
JA
de Vries
I Jolanda M
IJ
Wesseling
Pieter
P
Adema
Gosse J
GJ
D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000276:immunology*; D054422:Chemokine CCL22 / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005909:Glioblastoma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis; D054398:Receptors, CCR4 / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015703:Antigens, CD; C515482:CCL22 protein, human; C515354:CCR4 protein, human; D054422:Chemokine CCL22; D054398:Receptors, CCR4