title: Cutting edge: epigenetic regulation of Foxp3 defines a stable population of CD4+ regulatory T cells in tumors from mice and humans.
abstract: CD4(+) regulatory T cells (Tregs) are critical for maintaining self-tolerance and function to prevent autoimmune disease. High densities of intratumoral Tregs are generally associated with poor patient prognosis, a correlation attributed to their broad immune-suppressive features. Two major populations of Tregs have been defined, thymically derived natural Tregs (nTregs) and peripherally induced Tregs (iTregs). However, the relative contribution of nTregs versus iTregs to the intratumoral Treg compartment remains controversial. Demarcating the proportion of nTregs versus iTregs has important implications in the design of therapeutic strategies to overcome their antagonistic effects on antitumor immune responses. We used epigenetic, phenotypic, and functional parameters to evaluate the composition of nTregs versus iTregs isolated from mouse tumor models and primary human tumors. Our findings failed to find evidence for extensive intratumoral iTreg induction. Rather, we identified a population of Foxp3-stable nTregs in tumors from mice and humans.
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Waight
authors.affiliation: Oncology Section, Medical Affairs, Ono Pharmaceutical Co., Ltd., Osaka 541-8564, Japan;
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
authors.forename: Bo
authors.initials: B
authors.lastname: Marelli
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
authors.forename: Guozhong
authors.initials: G
authors.lastname: Qin
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Hance
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
authors.forename: Robert
authors.initials: R
authors.lastname: Tighe
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
authors.forename: Yan
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
authors.forename: Kin-Ming
authors.initials: KM
authors.lastname: Lo
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821;
authors.forename: Helen
authors.initials: H
authors.lastname: Sabzevari
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821; Robert.Hofmeister@EMDSerono.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Hofmeister
authors.affiliation: Immuno-Oncology Platform, EMD Serono Research and Development Institute, Billerica, MA 01821; Now Cancer Immunology Group, Agenus, Lexington, MA 02421.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta