TY  - JOUR
A1  - Sagiv, Jitka Y.
A1  - Michaeli, Janna
A1  - Assi, Simaan
A1  - Mishalian, Inbal
A1  - Kisos, Hen
A1  - Levy, Liran
A1  - Damti, Pazzit
A1  - Lumbroso, Delphine
A1  - Polyansky, Lola
A1  - Sionov, Ronit V.
A1  - Ariel, Amiram
A1  - Hovav, Avi-Hai
A1  - Henke, Erik
A1  - Fridlender, Zvi G.
A1  - Granot, Zvi
T1  - Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer
JF  - Cell Reports
N2  - Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro-and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs) that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs). LDNs consist of both immature myeloid-derived suppressor cells (MDSCs) and mature cells that are derived from HDNs in a TGF-beta-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.
KW  - tumorigenic properties
KW  - innate immunity
KW  - adenocarcinoma
KW  - inhibition
KW  - model
KW  - suppressor cells
KW  - tumor
KW  - TGF-beta
KW  - mice
KW  - lung
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144102
VL  - 10
IS  - 4
ER  - 
TY  - JOUR
A1  - Køllgaard, Tania
A1  - Ugurel-Becker, Selma
A1  - Idorn, Manja
A1  - Andersen, Mads Hald
A1  - Becker, Jürgen C.
A1  - Straten, Per thor
T1  - Pre-Vaccination Frequencies of Th17 Cells Correlate with Vaccine-Induced T-Cell Responses to Survivin-Derived Peptide Epitopes
JF  - PLoS One
N2  - Various subsets of immune regulatory cells are suggested to influence the outcome of therapeutic antigen-specific anti-tumor vaccinations. We performed an exploratory analysis of a possible correlation of pre-vaccination Th17 cells, MDSCs, and Tregs with both vaccination-induced T-cell responses as well as clinical outcome in metastatic melanoma patients vaccinated with survivin-derived peptides. Notably, we observed dysfunctional Th1 and cytotoxic T cells, i.e. down-regulation of the CD3\(\zeta\)chain (p=0.001) and an impaired IFN\(\gamma\)-production (p=0.001) in patients compared to healthy donors, suggesting an altered activity of immune regulatory cells. Moreover, the frequencies of Th17 cells (p=0.03) and Tregs (p=0.02) were elevated as compared to healthy donors. IL-17-secreting CD4\(^{+}\) T cells displayed an impact on the immunological and clinical effects of vaccination: Patients characterized by high frequencies of Th17 cells at pre-vaccination were more likely to develop survivin-specific T-cell reactivity post-vaccination (p=0.03). Furthermore, the frequency of Th17 (p=0.09) and Th17/IFN\(\gamma\)\(^{+}\) (p=0.19) cells associated with patient survival after vaccination. In summary, our explorative, hypothesis-generating study demonstrated that immune regulatory cells, in particular Th17 cells, play a relevant role for generation of the vaccine-induced anti-tumor immunity in cancer patients, hence warranting further investigation to test for validity as predictive biomarkers.
KW  - suppressor cells
KW  - melanoma patients
KW  - patient survival
KW  - cancer patients
KW  - Th17
KW  - tumor immunity
KW  - blood
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151509
VL  - 10
IS  - 7
ER  -